Risk Factors For Incident Fractures Research Articles

Serum branched-chain amino acid levels are associated with fracture risk in Japanese women.

Branched-chain amino acids (BCAAs) have been shown to exert beneficial effects on muscle and bone metabolism; however, no studies to date have investigated whether BCAAs have beneficial effects on bone fractures. Herein, we aim to prospectively investigate the relationship between serum BCAA concentrations and the occurrence of vertebral fractures (VFs) in Japanese women. During the observation period (7.5 ± 6.1 years), 188 of 983 participants experienced VF. Kaplan-Meier analyses were conducted to examine time-dependent variations in the vertebral compression fracture occurrence rate. Patients were stratified into quartiles based on serum BCAA concentration for this analysis. The analysis results indicated that the group with the lowest BCAA level developed VFs significantly earlier and with a higher frequency than the other groups (P < 0.001). A Cox proportional hazards model showed that BCAA concentration was a significant risk factor for incident fracture, even after adjusting for possible confounding factors. A series of multiple regression analyses were performed to identify factors related to serum BCAA concentration, with the results identifying levels of glycated hemoglobin (P < 0.001), adiponectin (P < 0.001), and NOx (P = 0.011) as significant factors associated with serum BCAA. Overall, the present study revealed that a lower serum BCAA level was an independent risk factor for incident VF in postmenopausal women. Geriatr Gerontol Int 2024; ••: ••-••.

Incidence of bone fractures among patients on maintenance hemodialysis

Background Patients with chronic kidney disease, especially those undergoing hemodialysis (HD), have a higher risk of fragility fractures. However, the magnitude of the problem and risk factors associated with fracture incidence have not been well studied in the Kingdom of Saudi Arabia. Methods This multicenter retrospective study involved HD centers in Jeddah from 2015 to 2021. This study included all adult HD patients. Patient demographics, medication usage, and clinical and biochemical parameters were collected from the registry records. Results The study included 328 patients on HD, with a mean age of 53 years. The median duration of HD was 47 months. Osteoporosis was found in 9% of the patients, and 8% had a previous parathyroidectomy. Over the observation period, fractures occurred in 32 patients, with an incidence rate of 20 case/1000 end stage kidney disease patients-year. Patients with fractures had a higher rate of osteoporosis, underwent more parathyroidectomy, had longer HD vintage, and higher bone-specific alkaline phosphatase (BSAP) levels. BSAP was the most significant predictor of fracture incidence in the regression analysis. Using a BSAP cutoff value of 96.6 µg/L, the sensitivity and specificity to predict fractures were 81.8% and 49%, respectively. Conclusion The main risk factors for incident fractures were osteoporosis, previous parathyroidectomy, longer HD vintage, and higher BSAP level. A higher BSAP score was the most significant predictor of incident fractures. This may highlight the importance of monitoring bone turnover markers and the negative impact of high bone turnover on patient health.

Time-Varying Risk Factors for Incident Fractures in Kidney Transplant Recipients: A Nationwide Cohort Study in South Korea.

Little is known about the time-varying risk factors for fractures in kidney transplant recipients (KTRs). Using the Korea Organ Transplantation Registry, a nationwide cohort study of KTRs, the incidence, locations, and time-varying predictors of fractures were analyzed, including at baseline and post-transplant 6-month variables in KTRs who underwent KT between January 2014 and June 2019. Among 4134 KTRs, with a median follow-up of 2.94 years (12,441.04 person-years), 63 patients developed fractures. The cumulative 5-year incidence was 2.10%. The most frequent locations were leg (25.40%) and foot/ankle (22.22%). In multivariable analysis, older recipient age at baseline (hazard ratio [HR], 1.035; 95% confidence interval [CI], 1.007-1.064; p = 0.013) and higher tacrolimus trough level (HR, 1.112; 95% CI, 1.029-1.202; p = 0.029) were associated with higher risks for fractures. Pretransplant diabetes mellitus had a time-dependent impact on fractures, with increasing risk as time elapses (HR for diabetes mellitus 1.115; 95% CI, 0.439-2.832; HR for diabetes mellitus × time, 1.049; 95% CI, 1.007-1.094; p = 0.022). In conclusion, KTRs had a high risk of peripheral skeletal fractures in the first 5 years. At baseline recipient age, pretransplant diabetes mellitus and tacrolimus trough level after KT were responsible for the fractures in KTRs.

Dietary Inflammatory Index and Fractures in Midlife Women: Study of Women's Health Across the Nation.

While evidence suggests that chronic, low-grade inflammation is a risk factor for bone loss and fractures, the potential relation between an inflammatory dietary profile and greater fracture risk is uncertain. We examined whether a more inflammatory diet, consumed during pre- and early perimenopause, is associated with more incident fractures starting in the menopause transition (MT) and continuing into postmenopause. Dietary inflammatory potential was quantified using 2 energy-adjusted dietary inflammatory index scores: one for diet only (E-DII), and one for diet plus supplements (E-DII-S). We included 1559 women from the Study of Women's Health Across the Nation, with E-DII and E-DII-S scores from the baseline visit (during pre- or early perimenopausal), and up to 20 years of follow-up. We excluded women using bone-beneficial medications at baseline; subsequent initiators were censored at first use. The associations of E-DII or E-DII-S (each tested as separate exposures) with incident fracture were examined using Cox proportional hazards regression. Adjusted for age, BMI, cigarette use, diabetes, MT stage, race/ethnicity, prior fracture, bone-detrimental medication use, aspirin or nonsteroidal anti-inflammatory drug use, and study site, greater E-DII and E-DII-S (tested separately) were associated with more future fractures. Each SD increment in E-DII and E-DII-S predicted 28% (P = .005) and 21% (P = .02) greater fracture hazard, respectively. Associations were essentially unchanged after controlling for bone mineral density. A more pro-inflammatory diet in pre- and early perimenopause is a risk factor for incident fracture. Future studies should consider whether reducing dietary inflammation in midlife diminishes fracture risk.

High serum miRNA 550a-5p levels are risk factors for incident fractures in older postmenopausal women with type 2 diabetes

Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)

Serum 25-Hydroxyvitamin D Level as an Independent Determinant of Quality of Life in Osteoporosis With a High Risk for Fracture

BackgroundDeteriorated quality of life (QOL) is a major problem in osteoporotic women. However, little is known regarding the determinants of QOL in patients with osteoporosis. ObjectiveOur aim was to explore the role of vitamin D status on QOL score in osteoporosis with high fracture risk. MethodsPatients were osteoporotic women aged ≥70 years and with ≥1 risk factor for incident fracture, namely prevalent osteoporotic fracture, bone mineral density (BMD) >–3.0 SD of young adult mean, or high bone turnover marker. Health-related QOL was assessed using the Japanese Osteoporosis Quality of Life Questionnaire (JOQOL). When patients were classified into quartiles by total QOL score). Serum 25-hydroxyvitamin D (25[OH]D) level was measured by immunoassay. ResultsA total of 1585 osteoporotic women were included in the study (age range, 70–95 years). Age, body mass index, serum 25(OH)D status (low, normal, or high), bone mineral density, number of prevalent vertebral fractures, presence of hypertension, presence of osteoarthritis, and history of falls were significantly correlated with QOL quartile. Multivariate liner regression analysis indicated that low serum 25(OH)D level (<20 ng/mL) was an independent determinant of total QOL score quartile (P = 0.0055). The conventional determinants of QOL—age (P < 0.0001), body mass index (P = 0.0060), number of prevalent vertebral fractures (P < 0.0001), presence of osteoarthritis (P = 0.0074), and history of fall (P = 0.0098)—were also independent determinants of total QOL score. ConclusionsThese results strongly suggest that low serum 25(OH)D level was a significant determinant of QOL in these osteoporotic women, independently of the conventional factors that reduce QOL. Maintenance of serum 25(OH)D levels >20 ng/mL may be required to maintain patients’ QOL in osteoporosis.

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.

Osteoporosis, frailty and fracture: implications for case finding and therapy

In almost all patients with incident fractures, the absolute risk of subsequent fracture and mortality is highest immediately after the fracture is incurred; the risk is substantially increased in frail elderly patients. The risk factors for incident fractures, such as bone fragility, tendency to fall and the presence of metabolic bone disease, remain underdiagnosed and undertreated. Here, we review the evidence that demonstrates the influence of these risk factors on susceptibility to subsequent fracture and mortality after an incident fracture, and discuss the tools available to predict these outcomes. In this Review, we also propose a systematic, coordinator-based approach to assessment of risk, allocation of treatment and follow-up in all patients over 50 years of age who present with a fracture. The aim of this proposed multistep procedure is to improve the prevention of secondary fracture, decrease mortality rates and reduce patient undertreatment or overtreatment.

Effects of alendronate plus alfacalcidol in osteoporosis patients with a high risk of fracture: the Japanese Osteoporosis Intervention Trial (JOINT) – 02

Objectives:The authors conducted a randomized controlled trial to clarify the efficacy and safety of alendronate plus alfacalcidol versus alendronate alone in a clinical setting.Research design and methods:Eligible patients were postmenopausal women with severe osteoporosis who were aged 70 years or older and had several risk factors for incident fractures. The primary endpoint was prevention of incident fractures, and the anti-fracture efficacy was evaluated in relation to the baseline serum 25(OH)D level.Results:A total of 2164 patients were randomized to alendronate plus alfacalcidol (combination therapy) or alendronate alone (monotherapy). Although the overall difference in the incidence of vertebral fracture between the two groups was not significant, the combination therapy group had a significantly reduced risk of vertebral fractures after the first 6 months (HR, 0.53). In subgroup analyses, the combination therapy group was superior in the strata of number of prevalent vertebral fractures of ≥2 (HR, 0.51) and grade 3 of prevalent vertebral fractures (HR, 0.55). The rate of non-vertebral weight-bearing bone fractures was significantly lower in the combination therapy group than in the monotherapy group during the follow-up period (HR, 0.31). A lower baseline 25(OH)D level was associated with a higher incidence of non-vertebral weight-bearing bone fractures (HR, 3.42) despite alendronate use. Although one patient given the combination therapy had mild hypercalcemia, serious hypercalcemia and unknown adverse events were not encountered. Because of the limitations presented in this study, these results may not apply to female patients with longer than 2 years of treatments, and to male osteoporosis patients.Conclusions:The combination therapy was no more effective for overall vertebral fracture prevention. However, subgroup analysis has shown that it was more effective for fracture prevention in patients with severe vertebral deformity, multiple prevalent vertebral fractures, and for non-vertebral weight-bearing bone fracture prevention.

Time since prior fracture is a risk modifier for 10-year osteoporotic fractures

The objective of this study was to assess the importance of time since prior fracture as a risk factor for future osteoporotic fractures and how it affects 10-year fracture rates. We identified 39,991 women 45 years of age or older undergoing baseline bone mineral density (BMD) testing (1990-2007) from a regional database that contains dual-energy X-ray absorptiometry (DXA) results for Manitoba, Canada. Health service records were used to identify nontrauma ICD-9-CM fracture codes preceding DXA, grouped as "major" fractures (n = 5178; hip, spine, forearm, and humerus) or "minor" fractures (n = 3479; ribs, sternum, pelvis, trunk, clavicle, scapula, patella, tibia/fibula, and ankle). Time since prior fracture was coded in years as less than 1, 1 to 5, 5 to 10, and more than 10. Incident fractures (ie, hip, spine, forearm, and humerus) after BMD testing were identified (mean follow-up 4.2 years, maximum 10 years) and studied in Cox proportional-hazards models adjusted for age, BMD T-score, and other covariates. After BMD testing, n = 1749 (4.4%) women experienced an incident fracture. Prior major fracture was a strong risk factor for incident fracture, greatest risk in the first year [hazard ratio (HR) 1.90, 95% confidence interval (CI) 1.60-2.25], declining by more than 10 years (HR 1.62, 95% CI 1.25-2.10). Prior minor fracture was a weaker risk factor, greatest in the first year (HR 1.45, 95% CI 1.13-1.87) and no longer significant by 1 to 5 years. Major and minor fractures both showed a time-dependent decline in importance as risk factors. In conclusion, time since prior fracture modifies future fracture risk, but prior fractures of the hip, spine, forearm, and humerus remain strong risk factors even 10 years later. Fracture risk assessment should emphasize the importance of prior fractures at these sites.

Risk factors associated with incident fractures in Japanese men with rheumatoid arthritis: a prospective observational cohort study

There are limited data in the literature concerning risk factors for incident fractures in men with rheumatoid arthritis (RA). We evaluated the association between potential risk factors and incident clinical fractures in male Japanese patients with RA. A total of 1050 male patients with RA were enrolled in a prospective, observational cohort study from 2000 to 2005. Participants were followed from 6 to 66 months (median follow-up, 48.7 months) and classified into three groups according to their incident fracture status from baseline: no new fracture, any new nonvertebral fracture, and new clinical vertebral fracture. The associations of potential risk factors were analyzed by Cox proportional hazards models. During follow-up, 30 patients (2.9%) developed a new nonvertebral fracture or a vertebral fracture. The baseline age, history of total knee replacement (TKR), and serum C-reactive protein (CRP) levels were associated with any nonvertebral fracture [baseline age: hazard ratio (HR), 1.08, 95% confidence interval (CI), 1.03-1.14; history of TKR: HR 6.02, 95% CI 1.19-30.42; and CRP: HR 0.60, 95% CI 0.38-0.95]. The baseline Japanese health assessment questionnaire (HAQ) score and daily dose of prednisolone were also associated with the incidence of clinical vertebral fractures (HR 7.74, 95% CI 2.10-28.48, and HR 1.28, 95% CI 1.14-1.45, respectively). Older age, history of TKR, and low serum CRP levels appear to be associated with any incident nonvertebral fracture in Japanese men with RA. High HAQ disability score and baseline doses of daily prednisolone may correlate with incident clinical vertebral fracture in Japanese men with RA.

Calcifications in the Abdominal Aorta Predict Fractures in Men: MINOS Study

In a cohort of 781 men >or=50 yr of age followed up for 10 yr, extended calcifications in the abdominal aorta were associated with a 2- to 3-fold increase in the risk of osteoporotic fractures regardless of BMD and falls. Cardiovascular disease and osteoporotic fractures are public health problems that frequently coexist. We assessed the relation of the severity of aortic calcifications with BMD and the risk of fracture in 781 men >or=50 yr of age. During a 10-year follow-up, 66 men sustained incident clinical fractures. Calcifications in the abdominal aorta expressed as an aortic calcification score (ACS) were assessed by a semiquantitative method. BMD was measured at the lumbar spine, hip, whole body, and distal forearm. ACS > 2 was associated with a 2-fold increase in the mortality risk after adjustment for age, weight, smoking, comorbidity, and medications. After adjustment for age, body mass index (BMI), smoking, and comorbidity, men in the highest quartile of ACS (>6) had lower BMD of distal forearm, ultradistal radius, and whole body than men in the lower quartiles. Log-transformed ACS predicted fractures when adjusted for age, BMI, age by BMI interaction, prevalent fractures, BMD, and history of two or more falls (e.g., hip BMD; OR = 1.44; p < 0.02). ACS, BMD at all the skeletal sites, and history of two or more falls were independent predictors of fracture. Men with ACS > 6 had a 2- to 3-fold increased risk of fracture after adjustment for confounding variables (OR = 2.54-3.04; p < 0.005-0.001 according to the site). This long-term prospective study showed that elevated ACS (>6) is a robust and independent risk factor for incident fracture in older men regardless of age, BMI, BMD, prevalent fractures, history of two or more falls, comorbidities, and medications.

Integrating a Gender Dimension into Osteoporosis and Fracture Risk Research

Sex (referring to the strict biological sense) and gender (referring to the sociocultural dimension) are major determinants of health and disease. This review examines similarities and differences between the sexes in the prevalence of osteoporosis and fractures, bone- and fall-related risk factors for incident fractures, and the possibilities of fracture prevention, as well as gender differences in the perception of osteoporosis. We reviewed recent English-language publications on sex and gender differences in the context of osteoporosis and fracture risk. We refer to several reviews that provide extensive reference lists on the topics discussed. The incidence of fractures is higher in boys than in girls. The burden of fractures in adults increases with age, and it starts earlier and is higher in adult women than in adult men. With life expectancy increasing, the annual number of fractures is likely to increase substantially. Fractures in adults contribute to increased mortality (more in men than in women), increased morbidity (equal in men and women), and high costs (greater for women than for men). Adult men experience fewer fractures than women do. Men build larger bones with better microarchitecture while they are growing and thereafter have less increase in bone remodeling. Furthermore, they develop bone loss at a later age. Compared with their female counterparts, fewer older men are hypogonadic, and life expectancy is shorter for men than for women. There are multiple reasons for the differences in the incidences of fractures between men and women, related to the many factors associated with both bone and falls that influence fracture risk from the molecular and cellular level to the organ level. Sex hormones play a central and essential role in the physiology of bone by direct and indirect mechanisms (eg, by interfering with the growth hormone and insulin-like growth factor-1 axis). Case-finding strategies to identify patients at highest risk for fractures, including bone densitometry and clinical risk factors, are much better documented at the population level in women than in men. Drug therapies that reduce the risk of a broad spectrum of fractures, even in the short term, are more clearly demonstrated in randomized controlled studies in women than in men. Drug therapy is more widely available for women with osteoporosis,but it is rarely given to men with osteoporosis. Differences in the perception of osteoporosis between men and women are even less well documented. In general, osteoporosis is underdiagnosed and undertreated in women but even more so in men, and is related to limits in the patient's and the physician's awareness at all clinical stages, from case finding to compliance with and persistence of therapy. Furthermore, the lay perception of a healthy lifestyle, the level of social isolation, networking within the health care system, and opportunities for screening appear to contribute to gender differences in participating in osteoporosis prevention and therapy. These aspects of health care deserve further attention and research.

Timing and risk factors for clinical fractures among postmenopausal women: a 5-year prospective study

BackgroundMany risk factors for fractures have been documented, including low bone-mineral density (BMD) and a history of fractures. However, little is known about the short-term absolute risk (AR) of fractures and the timing of clinical fractures. Therefore, we assessed the risk and timing of incident clinical fractures, expressed as 5-year AR, in postmenopausal women.MethodsIn total, 10 general practice centres participated in this population-based prospective study. Five years after a baseline assessment, which included clinical risk factor evaluation and BMD measurement, 759 postmenopausal women aged between 50 and 80 years, were re-examined, including undergoing an evaluation of clinical fractures after menopause. Risk factors for incident fractures at baseline that were significant in univariate analyses were included in a multivariate Cox survival regression analysis. The significant determinants were used to construct algorithms.ResultsIn the total group, 12.5% (95% confidence interval (CI) 10.1–14.9) of the women experienced a new clinical fracture. A previous clinical fracture after menopause and a low BMD (T-score <-1.0) were retained as significant predictors with significant interaction. Women with a recent previous fracture (during the past 5 years) had an AR of 50.1% (95% CI 42.0–58.1) versus 21.2% (95% CI 20.7–21.6) if the previous fracture had occurred earlier. In women without a fracture history, the AR was 13.8% (95% CI 10.9–16.6) if BMD was low and 7.0% (95% CI 5.5–8.5) if BMD was normal.ConclusionIn postmenopausal women, clinical fractures cluster in time. One in two women with a recent clinical fracture had a new clinical fracture within 5 years, regardless of BMD. The 5-year AR for a first clinical fracture was much lower and depended on BMD.