Higher dietary calcium intakes are associated with reduced risks of fractures, cardiovascular events, and mortality: a prospective cohort study of older men and women

The aim of this population-based, prospective cohort study was to investigate long-term associations between dietary calcium intake and fractures, non-fatal cardiovascular disease (CVD), and death from all causes. Participants were from the Melbourne Collaborative Cohort Study, which was established in 1990 to 1994. A total of 41,514 men and women (∼99% aged 40 to 69 years at baseline) were followed up for a mean (SD) of 12 (1.5) years. Primary outcome measures were time to death from all causes (n = 2855), CVD-related deaths (n = 557), cerebrovascular disease-related deaths (n = 139), incident non-fatal CVD (n = 1827), incident stroke events (n = 537), and incident fractures (n = 788). A total of 12,097 participants (aged ≥50 years) were eligible for fracture analysis and 34,468 for non-fatal CVD and mortality analyses. Mortality was ascertained by record linkage to registries. Fractures and CVD were ascertained from interview ∼13 years after baseline. Quartiles of baseline energy-adjusted calcium intake from food were estimated using a food-frequency questionnaire. Hazard ratios (HR) and odds ratios (OR) were calculated for quartiles of dietary calcium intake. Highest and lowest quartiles of energy-adjusted dietary calcium intakes represented unadjusted means (SD) of 1348 (316) mg/d and 473 (91) mg/d, respectively. Overall, there were 788 (10.3%) incident fractures, 1827 (9.0%) incident CVD, and 2855 people (8.6%) died. Comparing the highest with the lowest quartile of calcium intake, for all-cause mortality, the HR was 0.86 (95% confidence interval [CI] 0.76-0.98, ptrend  = 0.01); for non-fatal CVD and stroke, the OR was 0.84 (95% CI 0.70-0.99, ptrend  = 0.04) and 0.69 (95% CI 0.51-0.93, ptrend  = 0.02), respectively; and the OR for fracture was 0.70 (95% CI 0.54-0.92, ptrend  = 0.004). In summary, for older men and women, calcium intakes of up to 1348 (316) mg/d from food were associated with decreased risks for fracture, non-fatal CVD, stroke, and all-cause mortality.

Non-hip and non-vertebral fractures : the neglected fracture sites

Summary: Non-hip, non-vertebral fractures (NHNVF) were compared with hip, vertebral and controls. NHNVF were younger and heavier than controls and hip/vertebral fractures in both men and women, respectively. Falls and prior fractures were less common in NHNVF than hip fractures. Glucocorticoid use was lower in NHNVF compared to vertebral fracture (VF) in men. Introduction: Although hip fracture (HF) and vertebral fractures (VF) receive the most attention in the literature and are the targeted sites for fracture prevention, non-hip, non-vertebral fracture (NHNVF) sites account for a greater proportion of fractures than the hip or vertebrae. This study aimed to assess risk factors for NHNVF and compare them with those for HF, VF and controls. Methods: Incident fractures during 2005–2007 for men and 1994–1996 for women were identified using computerised keyword searches of radiological reports, and controls were selected at random from electoral rolls for participation in the Geelong Osteoporosis Study. Participants aged 60+ years were included in this study. Results: Compared to controls, men and women with NHNVF were younger (ORs, 0.90, 95 % CI 0.86–0.94; and 0.96, 0.93–0.98, respectively) and had a lower femoral neck bone mineral density (BMD) T-score (age-adjusted; difference [men] 0.383, P = 0.002; [women] 0.287, P = 0.001). Compared to HF, men and women with NHNVF were heavier (difference [men] 9.0 kg, P = 0.01; [women] 7.6 kg, P < 0.001). Heavier weight was also a risk factor for women with NHNVF compared to VF (1.03, 1.01–1.06). In men with NHNVF, falls (0.37, 0.14–0.97) and prior fractures (0.38, 0.15–0.98) were less common compared to HF; and glucocorticoid use was less common for NHNVF (0.30, 0.11–0.85) compared to VF. Conclusions: Given the high numbers of NHNVF sustained by men and women in this study, fracture prevention strategies should focus on individuals with high risk of sustaining these types of fractures, as well as on individuals who are more likely to sustain a HF or VF.

Association between hyperglycaemia and fracture risk in non-diabetic middle-aged and older Australians : a national, population-based prospective study (AusDiab)

Summary : The association between pre-diabetes and fracture risk remains unclear. In this large cohort of middle-aged and older Australian men and women without diabetes, elevated 2-h plasma glucose and pre-diabetes were associated with a reduced 5-year risk of low trauma and all fractures in women, independently of BMI, fasting insulin and other lifestyle factors.

Introduction : We aimed to (1) examine associations between fasting and 2-h plasma glucose (FPG and 2-h PG), fasting insulin and risk of low trauma and all fractures in non-diabetic adults and (2) compare fracture risk between adults with pre-diabetes (impaired glucose tolerance or impaired fasting glucose) and those with normal glucose tolerance (NGT).

Methods : Six thousand two hundred fifty-five non-diabetic men and women aged ≥40 years with NGT (n = 4,855) and pre-diabetes (n = 1,400) were followed for 5 years in the AusDiab Study. Fractures were self-reported.

Results : Five hundred thirty-nine participants suffered at least one fracture (368 women, 171 men), of which the majority (318) occurred after a low-energy trauma (258 women, 60 men). In women, a 2-h PG ≥7.2 mmol/L (highest quartile) was associated with a decreased risk of low trauma and all fractures independent of age and BMI [OR (95% CI) for low trauma fractures, 0.59 (0.40–0.88)], but also fasting insulin, smoking, physical activity, history of fracture, dietary calcium and alcohol intake or menopausal status. There was no effect of 2-h PG on fracture risk in men [OR (95% CI), 1.39 (0.60–3.26)] or any relationship between fracture risk and quartiles of FPG or insulin in either sex. Compared to women with NGT, those with pre-diabetes had a reduced risk of fracture [OR (95% CI) for all fractures, 0.70 (0.52–0.95); for low trauma fractures, 0.75 (0.53–1.05)].

Conclusion : Elevated 2-h PG levels and pre-diabetes were inversely associated with low trauma and/or all fractures in non-diabetic women, independent of BMI and fasting insulin levels.

Hormone therapy and risk of non-vertebral fracture : Geelong Osteoporosis Study

In this population-based study, we evaluated the association between exposure to hormone therapy (HT), bone mineral density (BMD) and the prevalence of non-vertebral fractures. The study was set in a region located in southeastern Australia where complete fracture ascertainment was determined from radiological reports. Current HT use for at least 6 months was ascertained in women with non-vertebral fractures [median age 70.9 years; inter-quartile range (IQR) 66.5–75.9 years] and randomly selected controls (median age 70.8 years; IQR 65.2–75.0 years). Current HT use was documented in 20 of 262 cases and 49 of 364 controls. The odds ratio (OR) for non-vertebral fracture associated with HT use was 0.53 (95% CI 0.31–0.92). HT use was associated with 2.6–7.5% higher BMD at axial and appendicular sites. HT use is associated with a halving of risk for non-vertebral fractures and higher BMD.

A randomised controlled trial of low-dose aspirin for the prevention of fractures in healthy older people : protocol for the ASPREE-Fracture substudy

Background Disability, mortality and healthcare burden from fractures in older people is a growing problem worldwide. Observational studies suggest that aspirin may reduce fracture risk. While these studies provide room for optimism, randomised controlled trials are needed. This paper describes the rationale and design of the ASPirin in Reducing Events in the Elderly (ASPREE)-Fracture substudy, which aims to determine whether daily low-dose aspirin decreases fracture risk in healthy older people. Methods ASPREE is a double-blind, randomised, placebo-controlled primary prevention trial designed to assess whether daily active treatment using low-dose aspirin extends the duration of disability-free and dementia-free life in 19 000 healthy older people recruited from Australian and US community settings. This substudy extends the ASPREE trial data collection to determine the effect of daily low-dose aspirin on fracture and fall-related hospital presentation risk in the 16 500 ASPREE participants aged ≥70 years recruited in Australia. The intervention is a once daily dose of enteric-coated aspirin (100 mg) versus a matching placebo, randomised on a 1:1 basis. The primary outcome for this substudy is the occurrence of any fracture-vertebral, hip and non-vert-non-hip-occurring post randomisation. Fall-related hospital presentations are a secondary outcome. Discussion This substudy will determine whether a widely available, simple and inexpensive health intervention-aspirin-reduces the risk of fractures in older Australians. If it is demonstrated to safely reduce the risk of fractures and serious falls, it is possible that aspirin might provide a means of fracture prevention.

New vertebral fractures after vertebroplasty: 2-year results from a randomised controlled trial

Summary: A randomised controlled trial of vertebroplasty (VP) versus placebo assessed the effect of VP on the risk of further vertebral fractures. While no statistically significant between-group differences for new or progressed fracture risk at 12 and 24 months were observed, we observed a consistent trend towards higher risk of any type of fracture in the group undergoing VP. Our analysis was underpowered, and further adequately powered studies are needed to be able to draw firm conclusions about further vertebral risk with vertebroplasty. Purpose: This study seeks to assess the effect of VP on the risk of further radiologically apparent vertebral fracture within two years of the procedure. Methods: We conducted a randomised placebo-controlled trial of VP in people with acute osteoporotic vertebral fracture. Eligible participants were randomly assigned to VP (n = 38) or placebo (n = 40). Cement volume and leakage were recorded for the VP group. Plain thoracolumbar radiographs were taken at baseline, 12 and 24 months. Two independent radiologists assessed these for new and progressed fractures at the same, adjacent and non-adjacent levels. Results: At 12 and 24 months, radiographs were available for 45 (58 %) and 47 (60 %) participants, respectively. There were no between-group differences for new or progressed fractures: 32 and 40 in the VP group after 12 and 24 months compared with 21 and 33 in the placebo group (hazard ratio (HR) 1.80, 95 % confidence interval (CI) 0.82 to 3.94). Similar results were seen when considering only adjacent (HR (95 % CI) 2.30 (0.57 to 9.29)) and non-adjacent (HR (95 % CI) 1.45 (0.55 to 3.81) levels. In all comparisons, there was a consistent trend towards higher risk of any type of fracture in the group undergoing VP. Within the VP group, fracture risk was unrelated to total (HR (95 % CI) 0.91 (0.71 to 1.17)) or relative (HR (95 % CI) 1.31 (0.15 to 11.48)) cement volume or cement leakage (HR (95 % CI) 1.20 (0.63 to 2.31)). Conclusion: For patients undergoing VP, our study did not demonstrate significant increases in subsequent fracture risk beyond that experienced by those with vertebral fractures who did not undergo the procedure. However, because of the non-significant numerical increases observed, studies with adequate power are needed to draw definite conclusions about fracture risk.

Humeral fractures in South-Eastern Australia: epidemiology and risk factors

In this study, we report the epidemiology and risk factors for humeral fractures (proximal humerus and shaft) among men and women residing in south-eastern Australia. Incident fractures during 2006 and 2007 were identified using X-ray reports (Geelong Osteoporosis Study Fracture Grid). Risk factors were identified using data from case-control studies conducted as part of the Geelong Osteoporosis Study. Median age of fracture was lower in males than females for proximal humerus (33.0 vs 71.2 years), but not for humeral shaft (8.9 vs 8.5 years). For females, proximal humerus fractures occurred mainly in the 70-79 and 80+ years age groups, whereas humeral shaft fractures followed a U-shaped pattern. Males showed a U-shaped pattern for both proximal humerus and humeral shaft fractures. Overall age-standardised incidence rates for proximal humerus fractures in males and females were 40.6 (95 % CI 32.7, 48.5) and 73.2 (95 % CI 62.2, 84.1) per 100,000 person years, respectively. For humeral shaft fractures, the age-standardised rate was 69.3 (95 % CI 59.0, 79.6) for males and 61.5 (95 % CI 51.9, 71.0) for females. There was an increase in risk of proximal humerus fractures in men with a lower femoral neck BMD, younger age, prior fracture and higher milk consumption. In pre-menopausal women, increased height and falls were both risk factors for proximal humerus fractures. For post-menopausal women, risk factors associated with proximal humerus fractures included a lower non-milk dairy consumption and sustaining a prior fracture. Humeral shaft fractures in both sexes were sustained mainly in childhood, while proximal humerus fractures were sustained in older adulthood. The overall age-standardised rates of proximal humerus fractures were nearly twice as high in females compared to males, whereas the incidence rates of humeral shaft fractures were similar.

Patients presenting with fractures are likely to be vitamin D deficient: are we getting enough sun?

BACKGROUND: 25-Hydroxyvitamin D serves a crucial role in bone metabolism through its role on osteoclast and osteoblastic function. To assess the implication of vitamin D and its relationship to bone fracture and fracture force, we have examined vitamin D levels in patients requiring inpatient fracture management. METHODS: We performed serological testing of vitamin D levels, calcium, parathyroid hormone and liver function tests on patients admitted to our rural institution in southeastern Australia for inpatient fracture management. All participants completed a questionnaire designed to screen for potential contributing factors to bony fragility. Demographic data were also obtained including age, gender and body mass index. Fracture location and the type of inpatient management as well as the force of injury were included in our analysis. RESULTS: We recruited 100 patients to the study, with a median age of 72 (range 22-98) of whom 66 were women. Most had low-energy fractures (79%), treated by internal fixation (73%) or arthroplasty (9%) with 18 treated non-operatively. The majority of the patients were at best vitamin D insufficient, <75 nmol/L (77%), and 38% were vitamin D deficient (<50 nmol/L). Only 14 patients had a formal diagnosis of osteoporosis at presentation, with 63 patients claiming daily sun exposure in line with recommendations for vitamin D sufficiency. CONCLUSIONS: Our data suggest that the prevalence of vitamin D insufficiency and deficiency is common in patients presenting with fractures in southeastern Australia and is not confined to elderly patients. All patients with fractures should be assessed for vitamin D levels and treated in accordance with vitamin D deficiency guidelines.