Lisa Langsetmo

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.

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.

Change in bone mineral density as a function of age in women and men and association with the use of antiresorptive agents

Background: Measurement of bone mineral density is the most common method of diagnosing and assessing osteoporosis. We sought to estimate the average rate of change in bone mineral density as a function of age among Canadians aged 25–85, stratified by sex and use of antiresorptive agents. Methods: We examined a longitudinal cohort of 9423 participants. We measured the bone mineral density in the lumbar spine, total hip and femoral neck at baseline in 1995–1997, and at 3-year (participants aged 40–60 years only) and 5-year follow-up visits. We used the measurements to compute individual rates of change. Results: Bone loss in all 3 skeletal sites began among women at age 40–44. Bone loss was particularly rapid in the total hip and was greatest among women aged 50–54 who were transitioning from premenopause to postmenopause, with a change from baseline of –6.8% (95% confidence interval [CI] –7.5% to –4.9%) over 5 years. The rate of decline, particularly in the total hip, increased again among women older than 70 years. Bone loss in all 3 skeletal sites began at an earlier age (25–39) among men than among women. The rate of decline of bone density in the total hip was nearly constant among men 35 and older and then increased among men older than 65. Use of antiresorptive agents was associated with attenuated bone loss in both sexes among participants aged 50–79. Interpretation: The period of accelerated loss of bone mineral density in the hip bones occurring among women and men older than 65 may be an important contributor to the increased incidence of hip fracture among patients in that age group. The extent of bone loss that we observed in both sexes indicates that, in the absence of additional risk factors or therapy, repeat testing of bone mineral density to diagnose osteoporosis could be delayed to every 5 years.

Dietary patterns and incident low-trauma fractures in postmenopausal women and men aged ≥50 y: a population-based cohort study

BACKGROUND Previous research has shown that dietary patterns are related to the risk of several adverse health outcomes, but the relation of these patterns to skeletal fragility is not well understood. OBJECTIVE Our objective was to determine the relation between dietary patterns and incident fracture and possible mediation of this relation by body mass index, bone mineral density, or falls. DESIGN We performed a retrospective cohort study based on the Canadian Multicentre Osteoporosis Study-a randomly selected population-based cohort. We assessed dietary patterns by using self-administered food-frequency questionnaires in year 2 of the study (1997-1999). Our primary outcome was low-trauma fracture occurring before the 10th annual follow-up (2005-2007). RESULTS We identified 2 dietary patterns by using factor analysis. The first factor (nutrient dense) was strongly associated with intake of fruit, vegetables, and whole grains. The second factor (energy dense) was strongly associated with intake of soft drinks, potato chips, French fries, meats, and desserts. The nutrient-dense factor was associated with a reduced risk of fracture per 1 SD in men overall [hazard ratio (HR): 0.83; 95% CI: 0.64, 1.08] and in women overall (HR: 0.86; 95% CI: 0.76, 0.98). An age trend (P = 0.03) was observed, which yielded an HR of 0.97 in younger women (age < 70 y) compared with an HR of 0.82 in older women (age ≥ 70 y). The associations were independent of body mass index, bone mineral density, falls, and demographic variables. The energy-dense pattern was not related to fracture. CONCLUSION A diet high in vegetables, fruit, and whole grains may reduce the risk of low-trauma fracture, particularly in older women.

Bone Mineral Density Predicts Fractures in Chronic Kidney Disease

Fractures are common in chronic kidney disease (CKD). The optimal methods by which to assess fracture risk are unknown, in part, due to a lack of prospective studies. We determined if bone mineral density (BMD) by dual‐energy X‐ray absorptiometry (DXA), and/or high‐resolution peripheral quantitative computed tomography (HRpQCT) could predict fractures in men and women ≥18 years old with stages 3 to 5 CKD. BMD was measured by DXA (at the total hip, lumbar spine, ultradistal, and 1/3 radius) and by HRpQCT (at the radius), and subjects were followed for 2 years for incident morphometric spine fractures and low‐trauma clinical fractures. The mean age of the subjects was 62 years with equal numbers having stages 3, 4, and 5 CKD. Over 2 years there were 51 fractures in 35 subjects. BMD by DXA at baseline was significantly lower at all sites among those with incident fractures versus those without. For example, the mean BMD at the total hip in those with incident fractures was 0.77 g/cm2 (95% confidence interval [CI], 0.73 to 0.80) and in those without fracture was 0.95 g/cm2 (95% CI, 0.92 to 0.98). Almost all baseline HRpQCT measures were lower in those with incident fracture versus those without. For example, volumetric BMD in those with incident fractures was 232 mg HA/cm3 (95% CI, 213 to 251) and in those without fracture was 317.6 mg HA/cm3 (95% CI, 306 to 329.1). Bone loss occurred in all subjects, but was significantly greater among those with incident fractures. Our data demonstrate that low BMD (by DXA and HRpQCT) and a greater annualized percent decrease in BMD are risk factors for subsequent fracture in men and women with predialysis CKD.

Dietary patterns in Canadian men and women ages 25 and older: relationship to demographics, body mass index, and bone mineral density

BackgroundPrevious research has shown that underlying dietary patterns are related to the risk of many different adverse health outcomes, but the relationship of these underlying patterns to skeletal fragility is not well understood. The objective of the study was to determine whether dietary patterns in men (ages 25-49, 50+) and women (pre-menopause, post-menopause) are related to femoral neck bone mineral density (BMD) independently of other lifestyle variables, and whether this relationship is mediated by body mass index.MethodsWe performed an analysis of 1928 men and 4611 women participants in the Canadian Multicentre Osteoporosis Study, a randomly selected population-based longitudinal cohort. We determined dietary patterns based on the self-administered food frequency questionnaires in year 2 of the study (1997-99). Our primary outcome was BMD as measured by dual x-ray absorptiometry in year 5 of the study (2000-02).ResultsWe identified two underlying dietary patterns using factor analysis and then derived factor scores. The first factor (nutrient dense) was most strongly associated with intake of fruits, vegetables, and whole grains. The second factor (energy dense) was most strongly associated with intake of soft drinks, potato chips and French fries, certain meats (hamburger, hot dog, lunch meat, bacon, and sausage), and certain desserts (doughnuts, chocolate, ice cream). The energy dense factor was associated with higher body mass index independent of other demographic and lifestyle factors, and body mass index was a strong independent predictor of BMD. Surprisingly, we did not find a similar positive association between diet and BMD. In fact, when adjusted for body mass index, each standard deviation increase in the energy dense score was associated with a BMD decrease of 0.009 (95% CI: 0.002, 0.016) g/cm2 for men 50+ years old and 0.004 (95% CI: 0.000, 0.008) g/cm2 for postmenopausal women. In contrast, for men 25-49 years old, each standard deviation increase in the nutrient dense score, adjusted for body mass index, was associated with a BMD increase of 0.012 (95% CI: 0.002, 0.022) g/cm2.ConclusionsIn summary, we found no consistent relationship between diet and BMD despite finding a positive association between a diet high in energy dense foods and higher body mass index and a strong correlation between body mass index and BMD. Our data suggest that some factor related to the energy dense dietary pattern may partially offset the advantages of higher body mass index with regard to bone health.

Physical activity, body mass index and bone mineral density-associations in a prospective population-based cohort of women and men: the Canadian Multicentre Osteoporosis Study (CaMos).

BACKGROUND Physical activity (PA) is an important modifiable risk factor for both bone mineral density (BMD) and body mass index (BMI). However, BMI is itself strongly predictive of BMD. Our aim was to determine the association between PA and BMD, with consideration of BMI as a potential mediating factor. METHODS The Canadian Multicentre Osteoporosis Study (CaMos) is a population-based prospective cohort study of Canadian women and men. PA was determined from interviewer-administered questionnaires at baseline and Year 5 and summarized as daily energy expenditure in total metabolic equivalents of the task multiplied by minutes/day (MET*m/d). Height, weight, and total hip and lumbar spine BMD were measured at baseline and Year 5. General linear models assessed relationships between PA and BMD, both cross-sectionally (baseline PA with baseline BMD) and longitudinally (average PA and change in PA with change in BMD). BMI was considered as a mediating factor. Potential confounders included age, center, education, caffeine intake, alcohol exposure, smoking history, history of weight-cycling, age at menarche, past use of oral contraceptives, history of >3 months missed menstruation, menopausal status, and antiresorptive use, as relevant. RESULTS The study included 2855 men and 6442 women. PA was inversely associated with BMI at baseline, and an increase in PA between baseline and Year 5 was associated with a decrease in BMI, with 0.41 (95% CI: 0.22, 0.60) kg/m(2) loss per 1000 MET*m/d increase (in men) and 0.40 (95% CI: 0.23, 0.57) kg/m(2) loss per 1000 MET*m/d increase (in women). BMI was strongly associated with BMD, both cross-sectionally and longitudinally. However, increased PA was associated with a small increase in total hip BMD, 0.004 (95% CI: 0.000-0.008) g/cm(2) per 1000 MET*m/d (in men) and 0.003 (95% CI: 0.000-0.007) g/cm(2) per 1000 MET*m/d (in women). Average PA was associated with an increase in lumbar spine BMD in women, but not in men; it was not associated with change in total hip BMD in either sex. CONCLUSION Increased PA is associated with an increase in BMD and a concomitant decrease in BMI. These findings suggest that population-level interventions to increase PA would favorably impact bone and other health outcomes.

Association Between Change in BMD and Fragility Fracture in Women and Men

Our objective was to estimate the relationship between longitudinal change in BMD and fragility fractures. We studied 3635 women and 1417 men 50–85 yr of age in the Canadian Multicentre Osteoporosis Study who had at least two BMD measurements (lumbar spine, femoral neck, total hip, and trochanter) within the first 5 yr of the study and fragility fractures (any, main, forearm/wrist, ribs, hip) within the first 7 yr. Multiple logistic regression was used to model the relationship between baseline BMD, BMD change, and fragility fractures. We found that, among nonusers of antiresorptives, independent of baseline BMD, a decrease of 0.01 g/cm2/yr in total hip BMD was associated with an increased risk of fragility fracture with ORs of 1.15 (95% CI: 1.01; 1.32) in women and 1.34 (95% CI: 1.02; 1.78) in men. The risk of fragility fractures in subgroups such as fast losers and those with osteopenia was better estimated by models that included BMD change than by models that included baseline BMD but excluded BMD change. Although the association between baseline BMD and fragility fractures was similar in users and nonusers of antiresorptives, the association was stronger in nonusers compared with users. These results show that BMD change in both men and women is an independent risk factor for fragility fractures and also predicts fracture risk in those with osteopenia. The results suggest that BMD change should be included with other variables in a comprehensive fracture prediction model to capture its contribution to osteoporotic fracture risk.

Repeat Low‐Trauma Fractures Occur Frequently Among Men and Women Who Have Osteopenic BMD

Fracture risk assessment based solely on BMD has limitations. Additional risk factors include the presence of a previous low‐trauma fracture. We sought to quantify the fracture burden attributable to first versus repeat fracture. We studied 2179 men and 5269 women, 50–90 yr of age, participating in the Canadian Multicentre Osteoporosis Study (CaMos). We included all low‐trauma fractures that occurred over 8 yr of follow‐up and classified these as either first or repeat clinical low‐trauma fracture based on lifetime fracture history. Analyses were further stratified by sex, age, BMD risk categories (normal, osteopenia, osteoporosis), and vertebral deformity status. There were 128 fractures in men and 577 fractures in women. About 25% of fractures in men and 40% in women were repeat fractures. Just over one half of first fractures occurred in those with osteopenic BMD (58% in men, 54% in women). Just under one half of repeat fractures also occurred in those with osteopenic BMD (42% in men, 47% in women). The incidence of repeat fracture was, in most cases, nearly double, but sometimes nearly quadruple, the incidence of first fracture within a given BMD risk category in both men and women. Repeat fractures contribute substantially to overall fracture burden, and the contribution is independent of BMD. Furthermore, those with a combination of prior low‐trauma fracture and another risk factor were at especially high risk of future fracture.

Kidney function and rate of bone loss at the hip and spine: the Canadian Multicentre Osteoporosis Study.

BACKGROUND The relationship between kidney function and bone loss is unclear. STUDY DESIGN A prospective observational study. SETTING & PARTICIPANTS 191 men and 444 women aged > or = 50 years participating in a population-based observational study designed to determine risk factors for bone loss and fractures. PREDICTORS The primary predictor of change in bone mineral density (BMD) was estimated creatinine clearance (using the Cockcroft-Gault formula) measured at baseline and stratified by quartiles. Our secondary predictor was estimated glomerular filtration rate using the Modification of Diet in Renal Disease Study equation, also stratified by quartiles. OUTCOMES & MEASUREMENTS Changes in BMD at the lumbar spine, total hip, and femoral neck during 5 years. RESULTS Compared with participants in the first quartile of estimated creatinine clearance (>101.2 mL/min), those in remaining quartiles were older (quartile 1, 50.0 years; quartile 2 [101.2-83.4 mL/min], 54.7 years; quartile 3 [83.4-68.3 mL/min], 60.5 years; and quartile 4 [<68.3 mL/min], 68.3 years); weighed less; reported more sedentary hours; were less likely to report excellent, very good, or good self-reported health; consumed less caffeine; and had lower serum calcium and phosphate and higher serum parathyroid hormone levels. After adjusting for age, weight, sex, baseline BMD, and these differences, compared with those in the first quartile, those in the fourth quartile had decreases in BMD of 0.08 g/cm(2) (95% CI, 0.04-0.1) at the lumbar spine, 0.08 g/cm(2) (95% CI, 0.06-0.1) at the femoral neck, and 0.09 g/cm(2) (95% CI, 0.07-0.1) at the total hip. Bone loss did not increase with worsening kidney function (P for trend > 0.05). Results were not substantially different using estimated glomerular filtration rate. LIMITATIONS Observational study design and indirect measures of kidney function. CONCLUSIONS Men and women with impaired kidney function are at increased risk of bone loss, even with minimal reduction in kidney function.