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.     

Serum 25‐hydroxyvitamin D and clinical fracture risk in a multiethnic cohort of women: The women's health initiative (WHI)

Low 25‐hydroxyvitamin D [25(OH)D] levels have been linked to hip fracture in white women. To study the association of 25(OH)D with risk of fracture in multiethnic women, we performed a nested case‐control study within the prospective Women's Health Initiative (WHI) Observational Study. Incident fractures were identified in 381 black, 192 Hispanic, 113 Asian, and 46 Native American women over an average of 8.6 years. A random sample of 400 white women who fractured was chosen. One control individual was selected per case and matched on age, race/ethnicity, and blood draw date. 25(OH)D, parathyroid hormone, and vitamin D–binding protein (DBP) were measured in fasting baseline serum. Conditional logistic regression models were used to calculate the odds ratio (OR) and 95% CI. In multivariable models, higher 25(OH)D levels compared with levels less than 20 ng/mL were associated with a lower risk of fracture in white women (20 to <30 ng/mL: OR = 0.82, 95% CI 0.58–1.16; ≤30.0 ng/mL: OR = 0.56, 95% CI 0.35–0.90; p trend = 0.02). In contrast, higher 25(OH)D (≥20 ng/mL) compared with levels less than 20 ng/mL were associated with a higher risk of fracture in black women (OR = 1.45, 95% CI 1.06–1.98; p trend = 0.043). Higher 25(OH)D (≥30.0 ng/mL) was associated with higher fracture risk in Asian women after adjusting for DBP (OR = 2.78, 95% CI 0.99–7.80; p trend = 0.04). There was no association between 25(OH)D and fracture in Hispanic or Native American women. Our results suggest divergent associations between 25(OH)D and fracture by race/ethnicity. The optimal level of 25(OH)D for skeletal health may differ in white and black women. © 2011 American Society for Bone and Mineral Research     

Secular Trends of Hip Fractures in Lebanon, 2006 to 2017: Implications for Clinical Practice and Public Health Policy in the Middle East Region

Country-specific hip fracture incidence rates (IRs) and longevity allow the Fracture Risk Assessment Tool (FRAX) to be adapted to individual countries. Secular trends can affect tool calibration. Data on hip fracture IRs in the Middle East is scarce, and long-term secular trend studies are nonexistent. Using the Ministry of Public Health hip fracture registry, we calculated age- and sex-specific hip fracture IRs in Lebanon, from 2006 to 2017, among individuals aged ≥50 years. We used Kendall's tau-b (τb) test to determine the correlation between time and hip fracture IRs, and calculated both the annual % change in IRs and the % change in IR compared to the baseline period (2006 to 2008). The registry recorded 6985 hip fractures, 74% at the femoral neck, 23% intertrochanteric, and 3% subtrochanteric. Men constituted 32% of the population, and were significantly younger than women (76.5 ± 11.0 years versus 77.7 ± 10.3 years; p < 0.001). Annual overall IRs, per 100,000, ranged from 126.6 in 2014 to 213.2 in 2017 in women, and 61.4 in 2015 to 111.7 in 2017 in men. The average women to men IR ratio was 1.8 (range, 1.5 to 2.1). IRs steadily increased with age, and IR ratios increased in parallel in both sexes, with a steeper and earlier rise (by 5 years) in women. Data showed a consistent decline in hip fracture IRs starting in 2006 in women, and in 2009 in men. There was a significant negative correlation between time (2006 to 2014) and hip fracture IRs in women (τb = −0.611, p = 0.022) but not in men (τb = −0.444, p = 0.095). The steady decrease in IRs reversed after 2015 in both sexes. This long-term data on secular trends in the Middle East is novel and consistent with worldwide changes in hip fracture rates. The impact of such changes on national FRAX-derived estimates is unclear, should be assessed, and may necessitate an update in the FRAX Lebanon calculator. © 2019 American Society for Bone and Mineral Research.     

Osteoporosis‐Related Health Services Utilization Following First Hip Fracture Among a Cohort of Privately‐Insured Women in the United States, 2008–2014: An Observational Study

Timely identification and treatment of osteoporosis following hip fracture is recommended to mitigate future fracture risk, yet prior work has demonstrated a disconnect between evidence‐based recommendations and real‐world implementation. We sought to describe contemporary patterns of osteoporosis screening and initiation of pharmacotherapy following hip fracture based on medical and pharmacy claims in the OptumLabs? Data Warehouse. From a national sample, we identified 8349 women aged 50+ years enrolled in private commercial or Medicare Advantage plans with no prior history of osteoporosis diagnosis, osteoporosis pharmacotherapy, or hip fracture who experienced a hip fracture between 2008 and 2013. Just 17.1% and 23.1% of these women had evidence of osteoporosis assessment and/or treatment within 6 or 12 months of their fractures, respectively. Women aged 80+ years were one‐third less likely to utilize recommended services within 6 months, compared to those aged 50 to 79 years (13.8% versus 20.8%; p < 0.001). Utilization of bone mass measurement increased significantly among women aged 65+ years over the study period (p < 0.001) while declining among those aged 50 to 64 years (p = 0.2). In contrast, rates of osteoporosis pharmacotherapy remained steady among women aged 50 to 64 years (p = 0.8) yet declined among women aged 65 to 79 years and aged 80+ years (p = 0.07 and p = 0.004, respectively). Accounting for differences in all measured characteristics, receipt of primary care was the strongest and most consistent predictor of osteoporosis assessment or treatment following fracture. © 2017 American Society for Bone and Mineral Research.     

Change in Trabecular Bone Score (TBS) With Antiresorptive Therapy Does Not Predict Fracture in Women: The Manitoba BMD Cohort

Bone mineral density (BMD) and trabecular bone score (TBS), along with additional clinical risk factors, can be used to identify individuals at high fracture risk. Whether change in TBS in untreated or treated women independently affects fracture risk is unclear. Using the Manitoba (Canada) DXA Registry containing all BMD results for the population we identified 9044 women age ≥40 years with two consecutive DXA scans and who were not receiving osteoporosis treatment at baseline (baseline mean age 62 ± 10 years). We examined BMD and TBS change, osteoporosis treatment, and incident major osteoporotic fractures (MOFs) for each individual. Over a mean of 7.7 years follow‐up, 770 women developed an incident MOF. During the interval between the two DXA scans (mean, 4.1 years), 5083 women initiated osteoporosis treatment (bisphosphonate use 80%) whereas 3961 women did not receive any osteoporosis treatment. Larger gains in both BMD and TBS were seen in women with greater adherence to osteoporosis medication (p for trend <0.001), and the magnitude of the increase was consistently greater for BMD than for TBS. Among treated women there was greater antifracture effect for each SD increase in total hip BMD change (fracture decrease 20%; 95% CI, 13% to 26%; p < 0.001), femoral neck BMD change (19%; 95% CI, 12% to 26%; p < 0.001), and lumbar spine BMD change (9%; 95% CI, 0% to 17%; p = 0.049). In contrast, change in TBS did not predict fractures in women who initiated osteoporosis treatment (p = 0.10). Among untreated women neither change in BMD or TBS predicted fractures. We conclude that, unlike antiresorptive treatment–related changes in BMD, change in lumbar spine TBS is not a useful indicator of fracture risk irrespective of osteoporosis treatment. © 2016 American Society for Bone and Mineral Research.     

Use of DXA‐based finite element analysis of the proximal femur in a longitudinal study of hip fracture

Bone mineral density (BMD) measured by dual‐energy X‐ray absorptiometry (DXA) is used for clinical assessment of fracture risk; however, measurements that incorporate bone strength could improve predictive ability. The aim of this study was to determine whether bone strength derived from finite element (FE) analysis was associated with hip fracture risk in a longitudinal study. We studied 728 women (mean age 82 years), 182 with subsequent hip fracture. FE models were generated from baseline DXA scans of the hip to determine femoral bone strength and load‐to‐strength ratio (LSR). The baseline LSR was significantly higher in fracture cases (median 1.1) compared with controls (0.7, p < 0.0001). Femoral strength and BMD were also significantly lower in cases (median 1820 N, 0.557 g/cm²) compared with controls (2614 N, 0.618 g/cm²) both p < 0.0001. Fracture risk increased per standard deviation decrease in femoral strength (odds ratio [OR] = 2.2, 95% confidence interval [CI] 1.8–2.8); femoral neck (FN) BMD (OR = 2.1, 95% CI 1.7–2.6); total hip BMD (OR = 1.8, 95% CI 1.5–2.1); and per SD increase in LSR (OR = 1.8, 95% CI 1.5–2.1). After adjusting for FN BMD, the odds ratio for femoral strength (OR = 1.7, 95% CI 1.2–2.4) and LSR (OR = 1.4, 95% CI 1.1–1.7) remained significantly greater than 1. The area under the curve (AUC) for LSR combined with FN BMD (AUC 0.69, 95% CI 0.64–0.73) was significantly greater than FN BMD alone (AUC 0.66, 95% CI 0.62–0.71, p = 0.004). Strength and LSR remained significant when adjusted for prevalent fragility fracture, VFA, and FRAX score. In conclusion, the DXA‐based FE model was able to discriminate incident hip fracture cases from controls in this longitudinal study independently from FN BMD, prior fracture, VFA, and FRAX score. Such an approach may provide a useful tool for better assessment of bone strength to identify patients at high risk of hip fracture who may benefit from treatment to reduce fracture risk. © 2013 American Society for Bone and Mineral Research.     

Long‐term cadmium exposure and the association with bone mineral density and fractures in a population‐based study among women

All people are exposed to cadmium (Cd) via food; smokers are additionally exposed. High Cd exposure is associated with severe bone damage, but the public health impact in relation to osteoporosis and fractures at low environmental exposure remains to be clarified. Within the population‐based Swedish Mammography Cohort, we assessed urinary Cd [U‐Cd, µg/g of creatinine (cr)] as a marker of lifetime exposure and bone mineral density (BMD) by dual‐energy X‐ray absorptiometry (DXA) among 2688 women. Register‐based information on fractures was retrieved from 1997 to 2009. Associations were evaluated by multivariable regression analyses. In linear regression, U‐Cd was inversely associated with BMD at the total body (p < .001), femoral neck (p = .025), total hip (p = .004), lumbar spine (p = .088), and volumetric femoral neck (p = .013). In comparison with women with U‐Cd < 0.50 µg/g of cr, those with U‐Cd ≥ 0.75 µg/g of cr had odds ratios (ORs) of 2.45 [95% confidence interval (CI) 1.51–3.97] and 1.97 (95% CI 1.24–3.14) for osteoporosis at the femoral neck and lumbar spine, respectively. Among never‐smokers, the corresponding ORs were 3.47 (95% CI 1.46–8.23) and 3.26 (95% CI 1.44–7.38). For any first fracture (n = 395), the OR was 1.16 (95% CI 0.89–1.50) comparing U‐Cd ≥ 0.50 µg/g of cr with lower levels. Among never‐smokers, the ORs (95% CIs) were 2.03 (1.33–3.09) for any first fracture, 2.06 (1.28–3.32) for first osteoporotic fracture, 2.18 (1.20–3.94) for first distal forearm fracture, and 1.89 (1.25–2.85) for multiple incident fractures. U‐Cd at low environmental exposure from food in a general population of women showed modest but significant association with both BMD and fractures, especially in never‐smokers, indicating a larger concern than previously known. © 2011 American Society for Bone and Mineral Research.     

Temporal Trends in Obesity,Osteoporosis Treatment,Bone Mineral Density,and Fracture Rates: A Population‐Based Historical Cohort Study

Diverging international trends in fracture rates have been observed, with most reports showing that fracture rates have stabilized or decreased in North American and many European populations. We studied two complementary population‐based historical cohorts from the Province of Manitoba, Canada (1996–2006) to determine whether declining osteoporotic fracture rates in Canada are attributable to trends in obesity, osteoporosis treatment, or bone mineral density (BMD). The Population Fracture Registry included women aged 50 years and older with major osteoporotic fractures, and was used to assess impact of changes in osteoporosis treatment. The BMD Registry included all women aged 50 years and older undergoing BMD tests, and was used to assess impact of changes in obesity and BMD. Model‐based estimates of temporal changes in fracture rates (Fracture Registry) were calculated. Temporal changes in obesity and BMD and their association with fracture rates (BMD Registry) were estimated. In the Fracture Registry (n = 27,341), fracture rates declined 1.6% per year (95% confidence interval [CI], 1.3% to 2.0%). Although osteoporosis treatment increased from 5.6% to 17.4%, the decline in fractures was independent of osteoporosis treatment. In the BMD Registry (n = 36,587), obesity increased from 12.7% to 27.4%. Femoral neck BMD increased 0.52% per year and lumbar spine BMD increased 0.32% per year after covariate adjustment (p < 0.001). Major osteoporotic fracture rates decreased in models that did not include femoral neck BMD (fully adjusted annual change –1.8%; 95% CI, –2.9 to –0.5), but adjusting for femoral neck BMD accounted for the observed reduction (annual change –0.5%; 95% CI, –1.8 to +1.0). In summary, major osteoporotic fracture rates declined substantially and linearly from 1996 to 2006, and this was explained by improvements in BMD rather than greater rates of obesity or osteoporosis treatment. © 2014 American Society for Bone and Mineral Research.     

Risk Factors for Treatment Failure With Antiosteoporosis Medication: The Global Longitudinal Study of Osteoporosis in Women (GLOW)

Antiosteoporosis medication (AOM) does not abolish fracture risk, and some individuals experience multiple fractures while on treatment. Therefore, criteria for treatment failure have recently been defined. Using data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), we analyzed risk factors for treatment failure, defined as sustaining two or more fractures while on AOM. GLOW is a prospective, observational cohort study of women aged ≥55 years sampled from primary care practices in 10 countries. Self‐administered questionnaires collected data on patient characteristics, fracture risk factors, previous fractures, AOM use, and health status. Data were analyzed from women who used the same class of AOM continuously over 3 survey years and had data available on fracture occurrence. Multivariable logistic regression was used to identify independent predictors of treatment failure. Data from 26,918 women were available, of whom 5550 were on AOM. During follow‐up, 73 of 5550 women in the AOM group (1.3%) and 123 of 21,368 in the non‐AOM group (0.6%) reported occurrence of two or more fractures. The following variables were associated with treatment failure: lower Short Form 36 Health Survey (SF‐36) score (physical function and vitality) at baseline, higher Fracture Risk Assessment Tool (FRAX) score, falls in the past 12 months, selected comorbid conditions, prior fracture, current use of glucocorticoids, need of arms to assist to standing, and unexplained weight loss ≥10 lb (≥4.5 kg). Three variables remained predictive of treatment failure after multivariable analysis: worse SF‐36 vitality score (odds ratio [OR] per 10‐point increase, 0.85; 95% confidence interval [CI], 0.76–0.95; p = 0.004); two or more falls in the past year (OR, 2.40; 95% CI, 1.34–4.29; p = 0.011), and prior fracture (OR, 2.93; 95% CI, 1.81–4.75; p < 0.0001). The C statistic for the model was 0.712. Specific strategies for fracture prevention should therefore be developed for this subgroup of patients. © 2014 American Society for Bone and Mineral Research.     

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, p_trend = 0.01); for non‐fatal CVD and stroke, the OR was 0.84 (95% CI 0.70–0.99, p_trend = 0.04) and 0.69 (95% CI 0.51–0.93, p_trend = 0.02), respectively; and the OR for fracture was 0.70 (95% CI 0.54–0.92, p_trend = 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. © 2015 American Society for Bone and Mineral Research.     

Hepatitis C Co‐infection and Severity of Liver Disease as Risk Factors for Osteoporotic Fractures Among HIV‐Infected Patients

Osteoporosis is increasingly reported in the aging HIV‐positive population, and co‐infection with hepatitis C virus (HCV) may further increase the risk of osteoporosis. However, it remains unclear whether HCV‐related increased fracture risk is a function of the severity of liver disease. We calculated the time‐updated alanine aminotransferase to platelet ratio index (APRI) score (an indirect marker of hepatic fibrosis) in all HIV‐infected patients enrolled in the Veterans Affairs' Clinical Case Registry between 1984 and 2009. The association between HCV co‐infection and incident osteoporotic fracture (defined as closed wrist, vertebral, or hip fracture) was assessed in univariate and multivariate Cox survival models adjusting for traditional risk factors for osteoporosis and APRI score or the presence of cirrhosis. A total of 772 osteoporotic fractures were identified among 56,660 HIV‐infected patients (98.1% male; 31.3% HCV co‐infected; median age 44.0 years) contributing 305,237 patient‐years of follow‐up. Fracture rates were significantly higher among HIV/HCV patients than HIV‐only patients (2.57 versus 2.07/1000 patient‐years, relative risk = 1.24, p < 0.0001). In a Cox multivariable model including age, race, smoking, drug use, body mass index, and antiretroviral therapy, HCV co‐infection remained an independent predictor of osteoporotic fractures after controlling for presence of cirrhosis (hazard ratio [HR] = 1.32; p < 0.001) or APRI score (HR = 1.30; p = 0.003). Among HIV/HCV co‐infected patients, cirrhosis strongly predicted osteoporotic fractures (HR = 1.65; 95% confidence interval [CI] 1.11–2.44; p = 0.012), but APRI score was a weaker predictor (HR = 1.008; 95% CI 1.002–1.014; p = 0.015). In conclusion, among HIV‐infected patients, severity of liver disease partly explains the HCV‐associated increased risk of osteoporotic fractures. Other determinants of this increased risk remain to be defined. © 2013 American Society for Bone and Mineral Research.     

Effects of antiresorptive treatment on nonvertebral fracture outcomes

Various definitions of nonvertebral fracture have been used in osteoporosis trials, precluding comparisons of efficacy. Using only subgroups of nonvertebral fractures for trial outcomes may underestimate the benefits and cost‐effectiveness of treatments. The objectives of this study were to determine (1) the effect of antiresorptive treatment on various nonvertebral fracture outcomes, (2) whether risk reduction from antiresorptive treatment is greater for nonvertebral fractures that have stronger associations with low BMD, and (3) sample size estimates for clinical trials of osteoporosis treatments. Study‐level data were combined from five randomized fracture‐prevention trials of antiresorptive agents that reduce the risk of nonvertebral fracture in postmenopausal women: alendronate, clodronate, denosumab, lasofoxifene, and zoledronic acid. Pooled effect estimates were calculated with random‐effects models. The five trials included 30,118 women; 2997 women had at least one nonvertebral fracture. There was no significant heterogeneity between treatments for any outcome (all p > 0.10). Antiresorptive treatment had similar effects on all fractures (summary hazard ratio [HR] = 0.76, 95% CI 0.70–0.81), high‐trauma fractures (HR = 0.74, 95% CI 0.57–0.96), low‐trauma fractures (HR = 0.77, (95% CI 0.71–0.83), nonvertebral six (ie, hip, pelvis, leg, wrist, humerus, and clavicle) fractures (HR = 0.73, 95% CI 0.66–0.80), other than nonvertebral six fractures (HR = 0.78, 95% CI 0.70–0.87), and all fractures other than finger, face, and toe (HR = 0.75, 95% CI 0.70–0.81). Risk reduction was not greater for fractures with stronger associations with low BMD (p = 0.77). A trial of all nonvertebral fractures would require fewer participants (n = 2641 per arm) than one of a subgroup of six fractures (n = 3289), for example. In summary, antiresorptive treatments reduced all nonvertebral fractures regardless of degree of trauma or special groupings, supporting the use of all nonvertebral fractures as a standard endpoint of osteoporosis trials and the basis for estimating the benefits and cost‐effectiveness of treatments. © 2011 American Society for Bone and Mineral Research     

Impact of the U.S. Food and Drug Administration's Safety‐Related Announcements on the Use of Bisphosphonates After Hip Fracture

The U.S. Food and Drug Administration (FDA) issued several announcements related to potential risk of bisphosphonates including osteonecrosis of the jaw (2005), atrial fibrillation (2007), and atypical femur fracture (2010). We aimed to evaluate the impact of three FDA drug safety announcements on the use of bisphosphonates in patients with hip fracture using claims data from a U.S. commercial health plan (2004‐2013). We calculated the proportion of patients in each quarter who received a bisphosphonate or other osteoporosis medication in the 6 months following hospitalization for hip fracture. Segmented logistic regression models examined the time trends. Among 22,598 patients with hip fracture, use of bisphosphonate decreased from 15% in 2004 to 3% in the last quarter of 2013. Prior to the 2007 announcement, there was a 4% increase in the odds of bisphosphonate use every quarter (OR 1.04; 95% CI, 1.02 to 1.07). After the 2007 announcement, there was a 4% decrease in the odds of bisphosphonate use (OR 0.96; 95% CI, 0.93 to 0.99) every quarter. The announcement in 2007 was associated with a significant decline in the rate of change of bisphosphonate uses over time (p < 0.001), but no impact on other osteoporosis medication use (p = 0.2). After the 2010 announcement, the odds of bisphosphonate use continued to decrease by 4% (OR 0.96; 95% CI, 0.94 to 0.98) each quarter and the odds of other osteoporosis medication use remained stable over time (OR 0.99; 95% CI, 0.96 to 1.02). The FDA safety announcement related to atrial fibrillation in 2007 was significantly associated with a decrease in bisphosphonate use among patients with hip fracture. © 2016 American Society for Bone and Mineral Research.     

Hospitalized osteoporotic vertebral fracture increases the risk of stroke: A population‐based cohort study

The association between osteoporosis and cardiovascular diseases has been demonstrated. Higher cardiovascular risk has also been correlated with vertebral fractures. However, the association between osteoporotic vertebral fracture and the possibly higher risk of stroke remains uncertain. This study aimed to evaluate the incidence, risk, and type of stroke in patients with osteoporotic vertebral fracture. Patients with osteoporotic vertebral fracture were identified (n = 380) and 10 age‐ and sex‐matched controls per case (comparison group, n = 3795) were chosen from a nationwide representative cohort of 999,997 people from 1998 to 2005. Both groups were followed‐up for stroke events for 3 years, matched by propensity scores with adjustments for covariates such as comorbidities (ie, hypertension, diabetes, arrhythmia, or coronary heart diseases) and exposure to medications (ie, aspirin, lipid lowering drug, or nitrates), and assessed by Kaplan‐Meier and Cox regression analyses. The incidence rate of stroke in the osteoporotic vertebral fracture group (37.5 per 1000 person‐years; 95% confidence interval [CI], 27.5–51.2) was significantly higher than in the comparison group (14.0 per 1000 person‐years; 95% CI, 12.0–16.4, p < 0.001). Stroke was more likely to occur in the osteoporotic vertebral fracture patients than in the normal controls (crude hazard ratio [HR] 2.68, 95% CI 1.89–3.79, p < 0.001; adjusted HR 2.71, 95% CI 1.90–3.86, p < 0.001). In conclusion, patients with osteoporotic vertebral fracture have a higher risk of stroke (ie, both ischemic and hemorrhagic) and require stroke prevention strategies. © 2013 American Society for Bone and Mineral Research.     

Bending Resistance at Hip and Fractures Risk in Postmenopausal Women Independent of Bone Mineral Density

Several studies suggest that aging loss of bone mass is not necessarily associated with reduced mechanical proprieties as bending resistance. Since postmenopausal women with fracture and without osteoporosis might have an impairment in the bending mechanisms at hip, our aim was to assess if women with and without fractures differ in the femoral parameters of resistance to bending, independent of the bone loss. In this cross-sectional study we enrolled 192 postmenopausal women who underwent X-ray absorptiometry scan to measure bone mineral density as well as cross-sectional geometry parameters at the hip (Hip structure analysis). Among women with osteoporosis, a higher odds ratio for fracture was found in the first tertile of NN-D_max, a parameter linked to the resistance to bending forces in a cross-section (tertile I, OR = 6.7, p = 0.03; CI 1.19–38.01; reference tertile III). We also found a significantly higher risk for major fracture in the first tertile of NN-D_max (tertile I, OR = 6.0, p = 0.02; CI 1.26?28.4; reference tertile III). Among women without osteoporosis, a significantly higher odds ratio for fracture was found in the first tertile of IT-CSA, a parameter of resistance to axial load (tertile I, OR = 7.2, p = 0.002; CI 2.04–25.9; reference tertile III). We also found a significantly higher risk for major fracture in the first tertile of IT-CSA (OR = 18.4, p = 0.001; CI 1.52?221.8; tertile III reference). We demonstrate that some hip structural parameters are independently associated to the fracture risk in postmenopausal women.     

Total and Visceral Adiposity Are Associated With Prevalent Vertebral Fracture in Women but Not Men at Age 62 Years: The Newcastle Thousand Families Study

Low body weight is an established risk factor for osteoporosis and fracture, but the skeletal risks of higher adiposity are unclear and appear sex‐specific and site‐dependent. The aim of this study was to investigate associations of total fat mass (TFM), visceral adipose tissue (VAT), and C‐reactive protein (CRP) with bone mineral density (BMD) and prevalent vertebral fracture (VF) in men and women aged 62 years. A total of 352 men and women aged 62.5 ± 0.5 years from the Newcastle Thousand Families Study cohort received dual‐energy X‐ray absorptiometry (DXA) evaluations of femoral neck and lumbar spine BMD, of the lateral spine for vertebral fracture assessment, and of the whole body for TFM and VAT (GE Lunar CoreScan, Madison, WI, USA). Plasma CRP, FRAX scores, falls in the last 12 months, and occupation at age 50 years were also included in the analysis. Vertebral fractures were less prevalent in women than in men (odds ratio [OR] = 0.33, p < 0.001) and BMD or FRAX scores did not differ between participants with and without VF. Women with VF were heavier and had higher TFM, VAT, and CRP than women without (p < 0.001). In women, greater (+1 SD) TFM and VAT increased the odds of any grade VF (TFM: OR = 1.06, p = 0.001; VAT: OR = 2.50, p = 0.002), and greater VAT mass increased the odds of prevalent mild VF (OR = 2.60, p = 0.002). In contrast, there were no associations in men. In both sexes, after controlling for body weight, neither VAT nor CRP were associated with BMD. In conclusion, irrespective of BMD, total and visceral adiposity were associated with prevalent VF in women but not in men. High fat mass, particularly if visceral, should be considered when assessing VF risk in women. Risk factors for VF in men require further investigation, particularly given their high prevalence. © 2017 American Society for Bone and Mineral Research.     

Risk of Incident Atrial Fibrillation With Zoledronic Acid Versus Denosumab: A Propensity Score–Matched Cohort Study

Zoledronic acid (ZA) is an effective agent in osteoporosis and malignancy-related bone disease but may be associated with increased risk of atrial fibrillation (AF), although current studies disagree on this risk. To examine the risk of incident AF among patients receiving ZA compared with denosumab in the first year of treatment, we performed a new-user, active comparator cohort study including privately insured Americans between January 1, 2010, and June 30, 2019. Individuals aged ≥50 years without known arrhythmia or advanced kidney disease who initiated ZA were 1:1 propensity score (PS)-matched to individuals initiating denosumab in separate osteoporosis and malignancy cohorts. The primary outcome was incident diagnosis of AF (≥ 1 inpatient or ≥ 2 outpatient diagnostic codes) over 1 year. Secondary outcomes included stroke/transient ischemic attack (TIA) and nonvertebral fracture. In the osteoporosis cohort (n = 16,235 pairs), mean age was 71 years, and 93% were female. There was higher risk of AF with ZA compared with denosumab over 1 year (incidence rate [IR] = 18.6 versus 14.9 per 1000 person-years; hazard ratio [HR] = 1.25; 95% confidence interval [CI] 1.04 to 1.50). In the malignancy cohort (n = 7732 pairs), mean age was 70 years, and 66% were female. There was a numerically higher, albeit not statistically significant, risk of AF with ZA compared with denosumab over 1 year (IR = 46.9 versus 39.0 per 1000 person-years; HR = 1.19; 95% CI 1.00 to 1.43; p = 0.06). No difference in stroke/TIA rates occurred. In the malignancy cohort, ZA was less effective than denosumab at preventing nonvertebral fractures (HR = 1.32; 95% CI 1.01 to 1.74). Compared with denosumab, ZA treatment for osteoporosis and possibly for malignancy-related bone disease is associated with modestly increased risk of incident AF in the first year of treatment. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Case-Control Study of the Pathogenesis and Sequelae of Symptomatic Vertebral Fractures in Men

To investigate the pathogenesis and sequelae of symptomatic vertebral fractures (VF) in men, we have performed a case–control study, comparing 91 men with VF (median age 64 years, range 27–79 years) with 91 age-matched control subjects. Medical history, clinical examination and investigations were performed in all patients and control subjects, to identify potential causes of secondary osteoporosis, together with bone mineral density (BMD) measurements. BMD was lower at the lumbar spine and all sites in the hip in patients with VF than in control subjects (p<0.001). Potential underlying causes of secondary osteoporosis were found in 41% of men with VF, compared with 9% of control subjects (OR 7.1; 95% CI 3.1–16.4). Oral corticosteroid and anticonvulsant treatment were both associated with a significantly increased risk of VF (OR 6.1; 95% CI 1.3–28.4). Although hypogonadism was not associated with an increased risk of fracture, the level of sex hormone binding globulin was higher (p<0.001) and the free androgen index lower (p<0.001) in men with VF than control subjects. Other factors associated with a significantly increased risk of VF were family history of bone disease (OR 6.1; 95% CI 1.3–28.4), current smoking (OR 2.8; 95% CI 1.2–6.7) and alcohol consumption of more than 250 g/week (OR 3.8; 95% CI 1.7–8.7). Men with VF were more likely to complain of back pain (p<0.001) and greater loss of height (p<0.001) than control subjects, and had poorer (p<0.001) scores for the energy, pain, emotion, sleep and physical mobility domains of the Nottingham Health Profile. We conclude that symptomatic VF in men are associated with reduced BMD, underlying causes of secondary osteoporosis such as corticosteroid and anticonvulsant treatment, family history of bone disease, current smoking and high alcohol consumption, and that they impair the perceived health of the individual. Received: 23 February 1998 / Accepted: 13 May 1998     

Assessment of incident spine and hip fractures in women and men using finite element analysis of CT scans

Finite element analysis of computed tomography (CT) scans provides noninvasive estimates of bone strength at the spine and hip. To further validate such estimates clinically, we performed a 5‐year case‐control study of 1110 women and men over age 65 years from the AGES‐Reykjavik cohort (case = incident spine or hip fracture; control = no incident spine or hip fracture). From the baseline CT scans, we measured femoral and vertebral strength, as well as bone mineral density (BMD) at the hip (areal BMD only) and lumbar spine (trabecular volumetric BMD only). We found that for incident radiographically confirmed spine fractures (n = 167), the age‐adjusted odds ratio for vertebral strength was significant for women (2.8, 95% confidence interval [CI] 1.8 to 4.3) and men (2.2, 95% CI 1.5 to 3.2) and for men remained significant (p = 0.01) independent of vertebral trabecular volumetric BMD. For incident hip fractures (n = 171), the age‐adjusted odds ratio for femoral strength was significant for women (4.2, 95% CI 2.6 to 6.9) and men (3.5, 95% CI 2.3 to 5.3) and remained significant after adjusting for femoral neck areal BMD in women and for total hip areal BMD in both sexes; fracture classification improved for women by combining femoral strength with femoral neck areal BMD (p = 0.002). For both sexes, the probabilities of spine and hip fractures were similarly high at the BMD‐based interventional thresholds for osteoporosis and at corresponding preestablished thresholds for “fragile bone strength” (spine: women ≤ 4500 N, men ≤ 6500 N; hip: women ≤ 3000 N, men ≤ 3500 N). Because it is well established that individuals over age 65 years who have osteoporosis at the hip or spine by BMD criteria should be considered at high risk of fracture, these results indicate that individuals who have fragile bone strength at the hip or spine should also be considered at high risk of fracture. © 2014 American Society for Bone and Mineral Research.