Protective Association of Milk Intake on the Risk of Hip Fracture: Results from the Framingham Original Cohort

Dairy foods are rich in bone‐beneficial nutrients, yet the role of dairy foods in hip fracture prevention remains controversial. Our objective was to evaluate the association of milk, yogurt, cheese, cream, and milk + yogurt intakes with incident hip fracture in the Framingham Original Cohort. A total of 830 men and women from the Framingham Original Cohort, a prospective cohort study, completed a food‐frequency questionnaire (1988 to 1989) and were followed for hip fracture until 2008. In this population‐based study, Cox‐proportional hazards regression was used to estimate hazard ratios (HR) by categories of energy‐adjusted dairy intake (servings/wk), adjusting for standard confounders and covariates. The exposure was energy‐adjusted intakes of milk, yogurt, cheese, cream, and milk + yogurt (servings/wk). Risk of hip fracture over the follow‐up was the primary outcome; the hypothesis being tested was formulated after data collection. The mean age at baseline was 77 years (SD 4.9, range 68 to 96). Ninety‐seven hip fractures occurred over the mean follow‐up time of 11.6 years (range 0.04 to 21.9 years). The mean ± SD (servings/wk) of dairy intakes at baseline were: milk = 6.0 ± 6.4; yogurt = 0.4 ± 1.3; cheese = 2.6 ± 3.1; and cream = 3.4 ± 5.5. Participants with medium (>1 and <7 servings/wk) or higher (≥7 servings/wk) milk intake tended to have lower hip fracture risk than those with low (≤1 serving/wk) intake (high versus low intake HR 0.58, 95% confidence interval [CI] 0.31–1.06, p = 0.078; medium versus low intake HR 0.61, 95% CI 0.36–1.08, p = 0.071; p trend = 0.178]. There appeared to be a threshold for milk, with 40% lower risk of hip fracture among those with medium/high milk intake compared with those with low intake (p = 0.061). A similar threshold was observed for milk + yogurt intake (p = 0.104). These associations were further attenuated after adjustment for femoral neck bone mineral density. No significant associations were seen for other dairy foods (p range = 0.117 to 0.746). These results suggest that greater intakes of milk and milk + yogurt may lower risk for hip fracture in older adults through mechanisms that are partially, but not entirely, attributable to effects on bone mineral density. © 2014 American Society for Bone and Mineral Research.     

The Effect of Fracture Recency on Observed 10-Year Fracture Probability: A Registry-Based Cohort Study

FRAX estimates 10-year fracture major osteoporotic fracture (MOF) and hip fracture probability from multiple risk factors. FRAX does not consider prior fracture site or time since fracture. Fracture risk is greater in the initial 2-year post-fracture period (imminent risk), implying that FRAX may underestimate risk in this setting. We used the population-based Manitoba Bone Mineral Density (BMD) Program registry to examine the effect of fracture recency and site on incident fracture risk predictions using FRAX. We identified women aged 40 years or older with baseline BMD and FRAX scores. Observed fracture outcomes to 10 years were compared with predicted 10-year fracture probability stratified by prior fracture status: none, recent (<2 years [median 0.3 years]), and remote (≥2 years [median 10.6 years]). For women with recent fractures, we also examined proposed multipliers to adjust FRAX for the effect of fracture recency and site. The cohort comprised 33,465 women aged 40 to 64 years (1897 recent fracture, 2120 remote fracture) and 33,806 women aged ≥65 years (2365 fracture, 4135 remote fracture). Observed fracture probability was consistent with predicted probability in most analyses. In women aged 40 to 64 years, there was a significant effect of recent vertebral and humerus fracture on MOF (observed to predicted 1.61 and 1.48, respectively), but these effects were still lower than the proposed multipliers (2.32 and 1.67, respectively). No significant effect of fracture recency was found after hip or forearm fracture in either age group. Our findings contribute to accumulating evidence of the importance of recent fracture. The effect of fracture recency was not consistent across fracture sites and with a lower magnitude than previously reported. Further quantification of effect size and specificity in additional independent cohorts is warranted to validate and refine recent-fracture multipliers in fracture risk assessment. © 2022 American Society for Bone and Mineral Research (ASBMR).     

Increased Mortality in Hip Fracture Patients Living Alone: A NOREPOS Study

Hip fracture is associated with excess mortality, persisting for many years after the fracture. Several factors may affect survival; however, the role of social support has been less studied. Living situation could be an indicator of a person's social support, which predicts mortality in the general population. In this longitudinal cohort study, we considered whether living alone was a risk factor for post-hip fracture mortality compared with living with a partner. Information on hip fractures from all hospitals in Norway from 2002 to 2013 was combined with the 2001 National Population and Housing Census. The association between living situation and mortality during 12.8 years of follow-up in 12,770 men and 22,067 women aged 50 to 79 years at fracture was investigated using flexible parametric survival analysis. We also estimated relative survival of hip fracture patients compared with that of the non-fractured background population in the same living situation (alone or with a partner). Higher mortality after hip fracture was found in both men and women living alone versus with a partner (hazard ratio [HR] men = 1.37, 95% confidence interval [CI] 1.29—1.44; HR women = 1.23, 95% CI 1.18—1.28, adjusting for age, education level, urbanization degree, and number of children). We demonstrated the strongest association in male hip fracture patients aged <60 years (long-term mortality HR = 3.29, 95% CI 2.25—6.49). Compared with the general population, relative survival 8 years after a hip fracture was 43% in men and 61% in women living alone, whereas relative survival in those living with a partner was 51% in men and 67% in women. In conclusion, hip fracture patients who lived alone had higher mortality than those living with a partner and lower survival relative to the general population. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Risk Factors for Fracture in Middle‐Age and Older‐Age Men of African Descent

Although fracture rates are lower in individuals of African descent compared to individuals of European ancestry, morbidity and mortality following a fracture may be greater in individuals of African ancestry. However, fracture risk and associated clinical risk factors have not been well‐defined among African ancestry populations, especially among men of African ancestry. We used data collected from the Tobago Bone Health Study to examine potential clinical risk factors for incident fractures, including demographic information, anthropometric measurements, medical history, lifestyle factors, bone mineral density (BMD), and hip structural geometry. Among 1933 Afro‐Caribbean men aged ≥40 years at study entry (mean age: 57.2 ± 11.0 years), 65 reported at least one new fracture during 10 years of subsequent follow‐up. Younger age, mixed Afro‐Caribbean ancestry, prior fracture history, BMD, and hip structural geometry were statistically significant risk factors for incident fractures. A 1‐SD change in several skeletal parameters (hip BMD, cross‐sectional area, outer diameter, cortical thickness, and buckling ratio) were each associated with a 35% to 56% increase in incident fracture risk after adjusting for age. Men with a prior fracture history were three times more likely to experience a new fracture during follow‐up, and the association remained strong after adjusting for age, mixed Afro‐Caribbean ancestry, and skeletal parameters (hazard ratios ranged from 2.72 to 2.82). Our findings suggest that except for age, risk factors for fracture in men of African ancestry are similar to established risk factors in white populations. Prior fracture history is a powerful and independent risk factor for incident fractures among men of African ancestry and could easily be incorporated into clinical risk evaluation. © 2014 American Society for Bone and Mineral Research.     

Mediterranean Diet and Hip Fracture in Swedish Men and Women

A Mediterranean diet, known to have beneficial effects on cardiovascular health, may also influence the risk of hip fracture although previous studies present discrepant results. We therefore aimed to determine whether the rate of hip fracture was associated with degree of adherence to a Mediterranean diet. We combined two Swedish cohort studies consisting of 37,903 men and 33,403 women (total n = 71,333, mean age 60 years) free of previous cardiovascular disease and cancer who answered a medical and a food‐frequency questionnaire in 1997. A modified Mediterranean diet score (mMED; range, 0 to 8 points) was created based on high consumption of fruits and vegetables, legumes and nuts, whole grains, fermented dairy products, fish, and olive/rapeseed oil, moderate intake of alcohol, and low intake of red and processed meat. Incident hip fractures between January 1, 1998, and December 31, 2012, were retrieved from the National Patient Register. Hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for potential confounders were calculated using Cox proportional hazards regression. Differences in age at hip fracture were calculated using multivariable Laplace regression. During follow‐up, 3175 hip fractures occurred at a median age of 73.3 years. One unit increase in the mMED was associated with 6% lower hip fracture rate (adjusted HR = 0.94; 95% CI, 0.92 to 0.96) and with a 3‐month higher median age at hip fracture (50th percentile difference = 2.8 months; 95% CI, 1.4 to 4.2). Comparing the highest quintile of adherence to the mMED (6 to 8 points) with the lowest (0 to 2 points) conferred an adjusted HR of hip fracture of 0.78 (95% CI, 0.69 to 0.89) and a 12‐month higher median age of hip fracture (50th percentile difference = 11.6 months; 95% CI, 4.2 to 19.0). Results were similar in men and women. We conclude that higher adherence to a Mediterranean‐like diet is associated with lower risk of future hip fracture. © 2016 American Society for Bone and Mineral Research.     

Relationship of Height to Site‐Specific Fracture Risk in Postmenopausal Women

Height has been associated with increased risk of fracture of the neck of femur. However, information on the association of height with fractures at other sites is limited and conflicting. A total of 796,081 postmenopausal women, who reported on health and lifestyle factors including a history of previous fractures and osteoporosis, were followed for 8 years for incident fracture at various sites by record linkage to National Health Service hospital admission data. Adjusted relative risks of fracture at different sites per 10‐cm increase in height were estimated using Cox regression. Numbers with site‐specific fractures were: humerus (3036 cases), radius and/or ulna (1775), wrist (9684), neck of femur (5734), femur (not neck) (713), patella (649), tibia and/or fibula (1811), ankle (5523), and clavicle/spine/rib (2174). The risk of fracture of the neck of femur increased with increasing height (relative risk [RR] = 1.48 per 10‐cm increase, 99% confidence interval [CI] 1.39–1.57) and the proportional increase in risk was significantly greater than for all other fracture sites (p_{heterogeneity} < 0.001). For the other sites, fracture risk also increased with height (RR = 1.15 per 10 cm, CI 1.12–1.18), but there was only very weak evidence of a possible difference in risk between the sites (p_{heterogeneity} = 0.03). In conclusion, taller women are at increased risk of fracture, especially of the neck of femur. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).     

U‐Shaped Association Between Serum 25‐Hydroxyvitamin D and Fracture Risk in Older Men: Results From the Prospective Population‐Based CHAMP Study

The aim of this population‐based, prospective, observational study was to examine the relationship between serum levels of 25‐hydroxyvitamin D (25OHD) and fracture risk in a cohort of 1662 community‐dwelling men aged 70 to 97 years followed for a mean of 4.3 years. Data about mobility, muscle strength, balance, medication use, cognition, medical history, lifestyle factors, renal function, and serum 25OHD were collected at baseline. Data on radiologically verified fractures were collected every 4 months. The relationship between fractures and serum 25OHD levels was analyzed using Cox's proportional hazard regression. We accounted for bone mineral density, falls, physical activity, sun exposure, and season of blood draw, in addition to anthropometric and lifestyle factors, medical history, muscle strength, balance, and medication and supplement use. There were 123 first‐incident fragility fractures. The relationship between baseline 25OHD and fracture risk was U‐shaped, with increased fracture risk in men with either low or high serum 25OHD levels. In multivariate analysis, the risk of fracture was greatest in men with 25OHD levels in the lowest quintile (25OHD ≤36 nmol/L; hazard ratio [HR] = 3.5; 95% confidence interval [CI] 1.7–7.0) and in men in the highest quintile (25OHD >72 nmol/L; HR = 2.7; 95% CI 1.4–5.4) compared with men in the 4th quintile (25OHD ≥60 to ≤72 nmol/L). These associations were not explained by lower BMD, increased physical activity, fall risk, or other lifestyle or anthropomorphic factors. In community‐dwelling older men, there appears to be a healthy target range for serum 25OHD concentrations. Thus, serum 25OHD levels too high and too low may be harmful in regard to fracture risk. © 2014 American Society for Bone and Mineral Research.     

Obstructive Sleep Apnea and Risk for Incident Vertebral and Hip Fracture in Women

Recent studies suggest a positive association between obstructive sleep apnea (OSA), a disorder associated with intermittent hypoxia and sleep fragmentation, and derangements in bone metabolism. However, no prospective study to date has investigated the association between OSA and fracture risk in women. We conducted a prospective study examining the relation between OSA and risk of incident vertebral fracture (VF) and hip fracture (HF) in the Nurses' Health Study. History of physician-diagnosed OSA was assessed by self-reported questionnaires. A previous validation study demonstrated high concordance between self-reports and medical record identification of OSA. OSA severity was further categorized according to the presence or absence of self-reported sleepiness. Self-reports of VF were confirmed by medical record review. Self-reported HF was assessed by biennial questionnaires. Cox proportional-hazards models estimated the hazard ratio for fracture according to OSA status, adjusted for potential confounders, including BMI, physical activity, calcium intake, history of osteoporosis, and falls, and use of sleep medications. Among 55,264 women without prior history of fracture, physician-diagnosed OSA was self-reported in 1.3% in 2002 and increased to 3.3% by 2012. Between 2002 and 2014, 461 incident VF cases and 921 incident HF cases were documented. The multivariable-adjusted hazard ratio (HR) for confirmed VF for women with history of OSA was 2.00 (95% CI, 1.29–3.12) compared with no OSA history, with the strongest association observed for OSA with daytime sleepiness (HR 2.86; 95% CI, 1.31–6.21). No association was observed between OSA history and self-reported HF risk (HR 0.83; 95% CI, 0.49–1.43). History of OSA is independently associated with higher risk of confirmed VF but did not have a statistically significant association with self-reported HF in women. Further research is warranted in understanding the role of OSA and intermittent hypoxia in bone metabolism and health that may differ by fracture site. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Leisure‐Time Physical Activity and Risk of Fracture: A Cohort Study of 66,940 Men and Women

Physical activity has been associated with reduced risk of fracture, but it is not known how the intensity or frequency of physical activity influences this risk reduction. We aim to compare the risk of hip fracture and fracture of any locale between men and women with different levels of leisure‐time walking/bicycling and exercise. A total of 37,238 women (born 1914–1948) from the Swedish Mammography Cohort and 45,906 men (born 1918–1952) from the Cohort of Swedish Men were followed for a maximum of 17 years. Exposure and covariate information was collected through a self‐administered questionnaire in 1997. Incident fractures (5153 individuals with hip fracture and 15,043 with any type of fracture) and comorbidities were gathered from national and local patient registries. Hazard ratios (HRs) were calculated using Cox proportional hazards regression. Individuals who walked/bicycled less than 20 minutes per day had a lower rate of hip fracture (multivariable adjusted HR = 0.77; 95% confidence interval [CI] 0.70 to 0.85) and any fracture (HR = 0.87; 95% CI 0.82 to 0.92) compared with those who hardly ever walked/bicycled. These reduced rates were also evident in both sexes, in different age categories, for vertebral fractures and for non‐hip, non‐vertebral fractures. Those who reported exercise 1 hour per week had a lower rate of hip fracture (HR = 0.87; 95% CI 0.80 to 0.96) and any fracture (HR = 0.94; 95% CI 0.89 to 0.99) compared with those who exercised less than 1 hour per week. Only minor differences in HRs were observed in individuals with moderate compared with higher levels of walking/bicycling or exercise. Walking/bicycling and exercise showed almost equal reductions in rate of fracture when compared with those in a joint category with lowest activity. In conclusion, both moderate and high self‐reported frequency of physical activity is associated with reduced future risk of fracture. © 2017 American Society for Bone and Mineral Research.     

Association Between Physical Activity and Risk of Fracture

Prospective studies that have examined the association between physical activity and fracture risks have reported conflicting findings. We performed a meta‐analysis to evaluate this association. We searched MEDLINE (1966 to February 1, 2013), EMBASE (1980 to February 1, 2013), and OVID (1950 to February 1, 2013) for prospective cohort studies with no restrictions. Categorical, heterogeneity, publication bias, and subgroup analyses were performed. There were 22 cohort studies with 1,235,768 participants and 14,843 fractures, including 8874 hip, 690 wrist, and 927 vertebral fractures. The pooled relative risk (RR) of total fractures for the highest versus lowest category of physical activity was 0.71 (95% confidence interval [CI], 0.63–0.80). The analysis of fracture subtypes showed a statistically significant inverse relationship between a higher category of physical activity and risk of hip and wrist fracture. The risk of hip or wrist fracture was 39% and 28% lower, respectively, among individuals with the highest category of physical activity than among those with the lowest category (95% CI, 0.54–0.69 and 0.49–0.96, respectively). The association between physical activity and vertebral fracture risk was not statistically related (RR, 0.87; 95% CI, 0.72–1.03). There was no evidence of publication bias. There was a statistically significant inverse association between physical activity and total fracture risk, especially for hip and wrist fractures. Additional subject‐level meta‐analyses are required for a more reliable assessment of subgroups and types of physical activity. © 2014 American Society for Bone and Mineral Research.     

Serum uric acid is associated with bone health in older men: A cross‐sectional population‐based study

Serum uric acid (UA) is a strong endogenous antioxidant. Since oxidative stress has been linked to osteoporosis, we examined the association between serum UA levels and bone mineral density (BMD), prevalent vertebral and nonvertebral fractures, and laboratory measures such as calcitropic hormones and bone turnover marker levels. This cross‐sectional analysis consisted of 1705 community‐dwelling men aged 70 years or over who participated in the baseline part of the Concord Health and Ageing in Men Project (CHAMP), a population‐based study of older men in Sydney, Australia. BMD at all sites was significantly higher among men with serum UA levels above the group median than among men with UA levels below the median. In multiple regression analyses adjusted for potential confounders, serum UA remained associated with BMD at all sites (β = 0.12 to 0.14, p < .001), serum calcium (β = 0.11, p = .001), parathyroid hormone (β = 0.09, p = .002), 25‐hydroxyvitamin D (β = 0.09, p = .005), and was negatively associated with urinary excretion amino‐terminal cross‐linked telopeptide of type 1 collagen (β = –0.09, p = .006). Overall, serum UA accounted for 1.0% to 1.44% of the variances in BMD (R² = 0.10 to 0.22). In multiple logistic regression analyses, above‐median serum UA levels were associated with a lower prevalence of osteoporosis at the femoral neck [odds ratio (OR) = 0.42, 95% confidence interval (CI) 0.22–0.81, p = .010) and lumbar spine (OR = 0.44, 95% CI 0.23–0.86, p = .016) and a lower prevalence of vertebral (OR = 0.62, 95% CI 0.43–0.91, p = .015) and nonvertebral (OR = 0.51, 95% CI 0.29–0.89, p = .018) fractures. In conclusion, higher serum UA levels are associated with higher BMD at all skeletal sites and with a lower prevalence of vertebral and nonvertebral fractures in older men. © 2011 American Society for Bone and Mineral Research.     

Height loss predicts subsequent hip fracture in men and women of the Framingham Study

Although height is a risk factor for osteoporotic fracture, current risk assessments do not consider height loss. Height loss may be a simple measurement that clinicians could use to predict fracture or need for further testing. The objective was to examine height loss and subsequent hip fracture, evaluating both long‐term adult height loss and recent height loss. Prospective cohort of 3081 adults from the Framingham Heart Study. Height was measured biennially since 1948, and cohort followed for hip fracture through 2005. Adult height loss from middle‐age years across 24 years and recent height loss in elderly years were considered. Cox proportional hazard regression was used to estimate association between height loss and risk of hip fracture. Of 1297 men and 1784 women, mean baseline age was 66 years (SD = 7.8). Average height loss for men was 1.06 inches (0.76), and for women was 1.12 inches (0.84). A total of 11% of men and 15% of women lost ≥2 inches of height. Mean follow‐up was 17 years, during which 71 men and 278 women had incident hip fractures. For each 1‐inch of height loss, hazard ratio (HR) = 1.4 in men [95% confidence interval (CI): 1.00, 1.99], and 1.04 in women (95% CI: 0.88, 1.23). Men and women who lost ≥2 inches of height had increased fracture risk (compared with 0 to <2 inches) of borderline significance: men HR = 1.8, 95% CI: 0.86, 3.61; women HR = 1.3, 95% CI: 0.90, 1.76. Recent height loss in elders significantly increased the risk of hip fracture, 54% in men and 21% in women (95% CI: 1.14, 2.09; 1.03, 1.42, respectively). Adult height loss predicted hip fracture risk in men in our study. Recent height loss in elderly men and women predicted risk of hip fracture. © 2012 American Society for Bone and Mineral Research     

Fracture risk in men with prostate cancer: A population‐based study

Fractures are increased among men with prostate cancer, especially those on androgen‐deprivation therapy (ADT), but few data are available on men with localized prostate cancer. The purpose of this investigation was to estimate fracture risk among unselected community men with prostate cancer and systematically assess associations with ADT and other risk factors for fracture. In a population‐based retrospective cohort study, 742 Olmsted County, MN, men with prostate cancer first diagnosed in 1990–1999 (mean age 68.2 ± 8.9 years) were followed for 6821 person‐years. We estimated cumulative fracture incidence, assessed relative risk by standardized incidence ratios, and evaluated risk factors in time‐to‐fracture regression models. All together, 482 fractures were observed in 258 men (71 per 1000 person‐years). Overall fracture risk was elevated 1.9‐fold, with an absolute increase in risk of 9%. Relative to rates among community men generally, fracture risk was increased even among men not on ADT but was elevated a further 1.7‐fold among ADT‐treated compared with untreated men with prostate cancer. The increased risk following various forms of ADT was accounted for mainly by associations with pathologic fractures (14% of all fractures). Among men not on ADT (62% of the cohort), more traditional osteoporosis risk factors were implicated. In both groups, underlying clinical characteristics prompting different treatments (indication bias) may have been partially responsible for the associations seen with specific therapies. To the extent that advanced‐stage disease and pathologic fractures account for the excess risk, the effectiveness of fracture prevention among men with prostate cancer may be limited. © 2011 American Society for Bone and Mineral Research     

The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT)

Zoledronic acid 5 mg (ZOL) annually for 3 years reduces fracture risk in postmenopausal women with osteoporosis. To investigate long-term effects of ZOL on bone mineral density (BMD) and fracture risk, the Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT) was extended to 6 years. In this international, multicenter, double-blind, placebo-controlled extension trial, 1233 postmenopausal women who received ZOL for 3 years in the core study were randomized to 3 additional years of ZOL (Z6, n = 616) or placebo (Z3P3, n = 617). The primary endpoint was femoral neck (FN) BMD percentage change from year 3 to 6 in the intent-to-treat (ITT) population. Secondary endpoints included other BMD sites, fractures, biochemical bone turnover markers, and safety. In years 3 to 6, FN-BMD remained constant in Z6 and dropped slightly in Z3P3 (between-treatment difference = 1.04%; 95% confidence interval 0.4 to 1.7; p = 0.0009) but remained above pretreatment levels. Other BMD sites showed similar differences. Biochemical markers remained constant in Z6 but rose slightly in Z3P3, remaining well below pretreatment levels in both. New morphometric vertebral fractures were lower in the Z6 (n = 14) versus Z3P3 (n = 30) group (odds ratio = 0.51; p = 0.035), whereas other fractures were not different. Significantly more Z6 patients had a transient increase in serum creatinine >0.5 mg/dL (0.65% versus 2.94% in Z3P3). Nonsignificant increases in Z6 of atrial fibrillation serious adverse events (2.0% versus 1.1% in Z3P3; p = 0.26) and stroke (3.1% versus 1.5% in Z3P3; p = 0.06) were seen. Postdose symptoms were similar in both groups. Reports of hypertension were significantly lower in Z6 versus Z3P3 (7.8% versus 15.1%, p < 0.001). Small differences in bone density and markers in those who continued versus those who stopped treatment suggest residual effects, and therefore, after 3 years of annual ZOL, many patients may discontinue therapy up to 3 years. However, vertebral fracture reductions suggest that those at high fracture risk, particularly vertebral fracture, may benefit by continued treatment.     

Circulating Levels of Carboxy‐Methyl‐Lysine (CML) Are Associated With Hip Fracture Risk: The Cardiovascular Health Study

Advanced glycation end products (AGE) in bone tissue are associated with impaired biomechanical properties and increased fracture risk. Here we examine whether serum levels of the AGE carboxy‐methyl‐lysine (CML) are associated with risk of hip fracture. We followed 3373 participants from the Cardiovascular Health Study (age 78 years; range, 68–102 years; 39.8% male) for a median of 9.22 years (range, 0.01–12.07 years). Rates of incident hip fracture were calculated by quartiles of baseline CML levels, and hazard ratios were adjusted for covariates associated with hip fracture risk. A subcohort of 1315 participants had bone mineral density (BMD) measurement. There were 348 hip fractures during follow‐up, with incidence rates of hip fracture by CML quartiles of 0.94, 1.34, 1.18, and 1.69 per 100 participant‐years. The unadjusted hazard ratio of hip fracture increased with each 1 SD increase (189 ng/mL) of CML level (hazard ratio, 1.27; 95% confidence interval [CI], 1.16–1.40]; p < 0.001). Sequential adjustment for age, gender, race/ethnicity, body mass index (BMI), smoking, alcohol consumption, prevalent coronary heart disease (CHD), energy expenditure, and estimated glomerular filtration rate (based on cystatin C), moderately attenuated the hazard ratio for fracture (1.17; 95% CI, 1.05–1.31; p = 0.006). In the cohort with BMD testing, total hip BMD was not significantly associated with CML levels. We conclude that increasing levels of CML are associated with hip fracture risk in older adults, independent of hip BMD. These results implicate AGE in the pathogenesis of hip fractures. © 2014 American Society for Bone and Mineral Research.     

Long‐Term Low Intake of Dietary Calcium and Fracture Risk in Older Adults With Plant‐Based Diet: A Longitudinal Study From the China Health and Nutrition Survey

The aim of this longitudinal study was to investigate long‐term associations between low dietary calcium intake and fracture risk in older adults with plant‐based diet. Data of self‐reported first fracture events of any type from 6210 Chinese men and women, aged 50 years or older and free from fracture at baseline, in a subcohort based on the China Health and Nutrition Survey (CHNS), were analyzed. Diet was repeatedly assessed by a combination of three consecutive 24‐hour individual dietary recalls and a weighing and measuring of household food inventory in each round. The older men and women habitually ingested mean (SD) of 415 (147) mg/d and 373 (140) mg/d of calcium from plant‐based diet, respectively. During a median follow‐up of 7.0 years, 127 men (4.34%) and 232 women (7.06%) experienced first fracture events. The crude rates were 4.88, 2.55, and 6.83 per 1000 person‐years at risk for men, and 6.72, 7.10, and 11.0 per 1000 person‐years at risk for women in the lowest, third, and highest quintile of dietary calcium intake. In nonlinear regressions, an increased risk of fracture was associated with dietary calcium intake more than 778 mg/d (multivariable adjusted hazard ratio [HR] 2.10, 95% confidence interval [CI] 1.00–4.41) or lower than 275 mg/d (1.74, 95% CI 1.00–3.01) for men and more than 651 mg/d for women (1.54, 95% CI 1.00–2.38). A nonsignificant trend of increase in fracture risk was found below 248 mg/d (1.00, 95% CI 0.67–1.50) in women using restricted cubic spline Cox regression. A relatively low fracture risk is observed in men with dietary calcium intakes of 275 to 780 mg/d and in women with intakes of 250 to 650 mg/d, and higher intakes may have no further benefit for fracture prevention. The patterns of dietary calcium with fracture risk are U‐shaped in men and possibly in women. © 2016 American Society for Bone and Mineral Research.     

Objectively‐Verified Parental Non‐Hip Major Osteoporotic Fractures and Offspring Osteoporotic Fracture Risk: A Population‐Based Familial Linkage Study

Parental hip fracture (HF) is associated with increased risk of offspring major osteoporotic fractures (MOFs; comprising hip, forearm, clinical spine or humerus fracture). Whether other sites of parental fracture should be used for fracture risk assessment is uncertain. The current study tested the association between objectively‐verified parental non‐hip MOF and offspring incident MOF. Using population‐based administrative healthcare data for the province of Manitoba, Canada, we identified 255,512 offspring with linkage to at least one parent (238,054 mothers and 209,423 fathers). Parental non‐hip MOF (1984–2014) and offspring MOF (1997–2014) were ascertained with validated case definitions. Time‐dependent multivariable Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs). During a median of 12 years of offspring follow‐up, we identified 7045 incident MOF among offspring (3.7% and 2.5% for offspring with and without a parental non‐hip MOF, p < 0.001). Maternal non‐hip MOF (HR 1.27; 95% CI, 1.19 to 1.35), paternal non‐hip MOF (HR 1.33; 95% CI, 1.20 to 1.48), and any parental non‐hip MOF (HR 1.28; 95% CI, 1.21 to 1.36) were significantly associated with offspring MOF after adjusting for covariates. The risk of MOF was even greater for offspring with both maternal and paternal non‐hip MOF (adjusted HR 1.61; 95% CI, 1.27 to 2.02). All HRs were similar for male and female offspring (all p_interaction >0.1). Risks associated with parental HF only (adjusted HR 1.26; 95% CI, 1.13 to 1.40) and non‐hip MOF only (adjusted HR 1.26; 95% CI, 1.18 to 1.34) were the same. The strength of association between any parental non‐hip MOF and offspring MOF decreased with older parental age at non‐hip MOF (p_trend = 0.028). In summary, parental non‐hip MOF confers an increased risk for offspring MOF, but the strength of the relationship decreases with older parental age at fracture. © 2016 American Society for Bone and Mineral Research.     

Direct costs of fractures in Canada and trends 1996–2006: A population‐based cost‐of‐illness analysis

Cost‐of‐illness (COI) analysis is used to evaluate the economic burden of illness in terms of health care resource (HCR) consumption. We used the Population Health Research Data Repository for Manitoba, Canada, to identify HCR costs associated with 33,887 fracture cases (22,953 women and 10,934 men) aged 50 years and older that occurred over a 10‐year period (1996–2006) and 101,661 matched control individuals (68,859 women and 32,802 men). Costs (in 2006 Canadian dollars) were estimated for the year before and after fracture, and the change (incremental cost) was modeled using quantile regression analysis to adjust for baseline covariates and to study temporal trends. The greatest total incremental costs were associated with hip fractures (median $16,171 in women and $13,111 for men), followed by spine fractures ($8,345 in women and $6,267 in men). The lowest costs were associated with wrist fractures ($663 in women and $764 in men). Costs for all fracture types were greater in older individuals (p < 0.001). Similar results were obtained with regression‐based adjustment for baseline factors. Some costs showed a slight increase over the 10 years. The largest temporal increase in women was for hip fracture ($13 per year, 95% CI $6–$21, p < 0.001) and in men was for humerus fracture ($11 per year, 95% CI $3–$19, p = 0.007). At the population level, hip fractures were responsible for the largest proportion of the costs after age 80, but the other fractures were more important prior to age 80. We found that there are large incremental health care costs associated with incident fractures in Canada. Identifying COI from HCR use offers a cost baseline for measuring the effects of evidence‐based guidelines implementation. © 2011 American Society for Bone and Mineral Research