Susceptibility genes for osteoporotic fracture in postmenopausal chinese women

To identify the susceptibility genes for osteoporotic fracture in postmenopausal Chinese women, a two‐stage case‐control association study using joint analysis was conducted in 1046 patients with nontraumatic vertebra, hip, or distal radius fractures and 2303 healthy controls. First, 113 single‐nucleotide polymorphisms (SNPs) in 16 potential osteoporosis candidate genes reported in recent genomewide association studies, meta‐analyses studies, large‐scale association studies, and functional studies were genotyped in a small‐sample‐size subgroup consisting of 541 patients with osteoporotic fractures and 554 healthy controls. Variants and haplotypes in SPTBN1, TNFRSF11B, CNR2, LRP4, and ESR1 that have been identified as being associated with osteoporotic fractures were further reanalyzed in the entire case‐control group. We identified one SNP in TNFRSF11B (rs3102734), three SNPs in ESR1 (rs9397448, rs2234693, and rs1643821), two SNPs in LRP4 (rs17790156 and rs898604), and four SNPs in SPTBN1 (rs2971886, rs2941583, rs2941584, and rs12475342) were associated with all of the broadly defined osteoporotic fractures. The most significant polymorphism was rs3102734, with increased risk of osteoporotic fractures (odds ratio, 1.35; 95% confidence interval [CI], 1.17–1.55, Bonferroni p = 2.6 × 10^?4). Furthermore, rs3102734, rs2941584, rs12475342, rs9397448, rs2234693, and rs898604 exhibited significant allelic, genotypic, and/or haplotypic associations with vertebral fractures. SNPs rs12475342, rs9397448, and rs2234693 showed significant genotypic associations with hip fractures, whereas rs3102734, rs2073617, rs1643821, rs12475342, and rs2971886 exhibited significant genotypic and/or haplotypic associations with distal radius fractures. Accordingly, we suggest that in addition to the clinical risk factors, the variants in TNFRSF11B, SPTBN1, ESR1, and LRP4 are susceptibility genetic loci for osteoporotic fracture in postmenopausal Chinese women. © 2012 American Society for Bone and Mineral Research © 2012 American Society for Bone and Mineral Research     

The risk of fracture in patients with multiple sclerosis: The UK general practice research

Patients with multiple sclerosis (MS) may be at an increased risk of fracture owing to a greater risk of falling and decreased bone mineral density when compared with the general population. This study was designed to estimate the relative and absolute risk of fracture in patients with MS. We conducted a population‐based cohort study using data from the UK General Practice Research Database linked to the National Hospital Registry (1997–2008). Incident MS patients (n = 5565) were matched 1:6 by year of birth, sex, and practice with patients without MS (controls). Cox proportional‐hazards models were used to derive adjusted hazard ratios (HRs) for fracture associated with MS. Time‐dependent adjustments were made for age, comorbidity, and drug use. Absolute 5‐ and 10‐year risks of fracture were estimated for MS patients as a function of age. Compared with controls, MS patients had an almost threefold increased risk of hip fracture [HR = 2.79, 95% confidence interval (CI) 1.83–4.26] and a risk of osteoporotic fracture that was increased 1.4‐fold (HR = 1.35, 95% CI 1.13–1.62). Risk was greater in patients who had been prescribed oral/intravenous glucocorticoids (GCs; HR = 1.85, 95% CI 1.14–2.98) or antidepressants (HR = 1.79, 95% CI 1.37–2.35) in the previous 6 months. Absolute fracture risks were low in younger MS patients but became substantial when patients were older than 60 years of age. It is concluded that MS is associated with an increased risk of fracture. Fracture risk assessment may be indicated in patients with MS, especially those prescribed GCs or antidepressants. © 2011 American Society for Bone and Mineral Research     

Serum 25‐hydroxyvitamin D and risk of major osteoporotic fractures in older U.S. adults

Results from previous prospective studies linking serum 25‐hydroxyvitamin D (25OHD) with fracture risk have been inconsistent. The present study examined the relationship between serum 25OHD and risk of incident major osteoporotic fracture (hip, spine, radius, and humerus) in older U.S. adults. The study used a pooled cohort of 4749 men and women ages 65 years and older from the third National Health and Nutrition Examination Survey (NHANES III, 1988–1994) and NHANES 2000–2004. Incident fractures were identified using linked mortality and Medicare records that were obtained for participants from both surveys. Serum 25OHD values were measured by radioimmunoassay in both surveys. Cox proportional hazards models were used to estimate the relative risk (RR) of fracture by serum 25OHD level. There were 525 incident major osteoporotic fractures (287 hip fractures) in the sample. Serum 25OHD was a significant linear predictor of major osteoporotic fracture and significant quadratic predictor of hip fracture in the total sample and among those with less than 10 years of follow‐up, but it was not related to risk of either fracture type among those with ≥10 years of follow‐up. Major osteoporotic fracture risk was increased by 26% to 27% for each SD decrease in serum 25OHD among those with less than 10 years of follow‐up. Serum 25OHD was significantly related to risk of major osteoporotic fractures as a group and to hip fracture alone in this cohort of older U.S. adults from NHANES III and NHANES 2000–2004. However, the predictive utility of serum 25OHD diminished after 10 years. In addition, the relationship appeared to be linear when major osteoporotic fracture risk was considered but quadratic when hip fracture risk was assessed. © 2013 American Society for Bone and Mineral Research.     

Evaluation of the FRAX and Garvan fracture risk calculators in older women

Fracture risk calculators estimate the absolute risk of osteoporotic fractures. We investigated the performance of the FRAX and Garvan Institute fracture risk calculators in healthy, older, New Zealand, postmenopausal women with normal bone mineral density (BMD) for their age. Fractures were ascertained in women initially enrolled in a 5‐year trial of calcium supplements and followed on average for 8.8 years. Baseline data (1422 women, mean age 74 years, mean femoral neck BMD T‐score –1.3) were used to estimate fracture risk during follow‐up using the FRAX and Garvan calculators. The FRAX–New Zealand tool was used both with and without baseline BMD. The discrimination of the calculators was assessed using the area under the curve (AUC) of receiver operating characteristic curves. The calibration was assessed by comparing estimated risk of fracture with fracture incidence across a range of estimated fracture risks and clinical factors. For each fracture subtype, the calculators had comparable moderate predictive discriminative ability (AUC range: hip fracture 0.67–0.70; osteoporotic fracture 0.62–0.64; any fracture 0.60–0.63) that was similar to that of models using only age and BMD. The Garvan calculator was well calibrated for osteoporotic fractures but overestimated hip fractures. FRAX with BMD underestimated osteoporotic and hip fractures. FRAX without BMD underestimated osteoporotic and overestimated hip fractures. In summary, none of the calculators provided better discrimination than models based on age and BMD, and their discriminative ability was only moderate, which may limit their clinical utility. The calibration varied, suggesting that the calculators should be validated in local cohorts before clinical use. © 2011 American Society for Bone and Mineral Research.     

Height loss in older women: Risk of hip fracture and mortality independent of vertebral fractures

We examined if height loss in older women predicts risk of hip fractures, other nonspine fractures, and mortality, and whether this risk is independent of both vertebral fractures (VFx) and bone mineral density (BMD) by dual‐energy X‐ray absorptiometry. Among 3124 women age 65 and older in the Study of Osteoporotic Fractures, we assessed the association with measured height change between year 0 (1986–1988) and year 15 (2002–2004) and subsequent risk of radiologically confirmed hip fractures, other nonspine fractures, and mortality assessed via death certificates. Follow‐up occurred every 4 months for fractures and vital status (>95% contacts complete). Cox proportional hazards models assessed risk of hip fracture, nonspine fracture, and mortality over a mean of 5 years after height change was assessed (ie, after final height measurement). After adjustment for VFx, BMD, and other potential covariates, height loss >5 cm was associated with a marked increased risk of hip fracture [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.06, 2.12], nonspine fracture (HR 1.48; 95% CI 1.20, 1.83), and mortality (1.45; 95% CI 1.21, 1.73). Although primary analyses were a subset of 3124 survivors healthy enough to return for a year 15 height measurement, a sensitivity analysis in the entire cohort (n = 9677) using initial height in earlier adulthood [self‐reported height at age 25 (?40 years) to measured height age >65 years (Year 0)] demonstrated consistent results. Height loss >5 cm (2″) in older women was associated with a nearly 50% increased risk of hip fracture, nonspine fracture, and mortality—independent of incident VFx and BMD. © 2012 American Society for Bone and Mineral Research     

Rapidly increasing rates of hip fracture in Beijing,China

The age‐specific rates of hip fractures have been declining in most countries in the West but a few studies suggest that the rates might be increasing in areas of Asia that are undergoing urbanization. We previously conducted a population‐based study of hip fracture rates in Beijing, China, in 1990 to 1992 that included validation of hip fracture cases. Using a similar approach to validate cases, we estimated the age‐specific hip fracture rates in Beijing, China, for 2002 to 2006. Specifically, we obtained hospital discharge data for hip fractures that were reported to the Beijing Bureau of Public Health. To confirm the diagnoses, Beijing residence, and find cases missed by the public records we checked individual cases in the public health records against medical records in a random sample of Beijing hospitals. The rates from public health data were adjusted for these under‐ and overestimations. We found that between 1990 and 1992 and 2002 and 2006, the adjusted age‐specific rates of hip fracture over age 50 years increased 2.76‐fold (95% confidence interval [CI], 2.68–2.84) in women and 1.61‐fold (95% CI, 1.56–1.66) in men. Over age 70 years, the age‐specific rates increased 3.37‐fold (95% CI, 3.28–3.47) in women and 2.01‐fold (95% CI, 1.95–2.07) in men. From 2002 to 2006, the rates over age 50 years increased 58% in women and 49% in men. We conclude that the rate of hip fracture has been rising very rapidly in Beijing, China. Therefore, the burden of hip fractures may be shifting rapidly from the West to urbanizing areas of the East. © 2012 American Society for Bone and Mineral Research     

Distribution of bone density in the proximal femur and its association with hip fracture risk in older men: The osteoporotic fractures in men (MrOS) study

This prospective case‐cohort study aimed to map the distribution of bone density in the proximal femur and examine its association with hip fracture. We analyzed baseline quantitative computed tomography (QCT) scans in 250 men aged 65 years or older, which comprised a randomly‐selected subcohort of 210 men and 40 cases of first hip fracture during a mean follow‐up period of 5.5 years. We quantified cortical, trabecular, and integral volumetric bone mineral density (vBMD), and cortical thickness (CtTh) in four quadrants of cross‐sections along the length of the femoral neck (FN), intertrochanter (IT), and trochanter (TR). In most quadrants, vBMDs and CtTh were significantly (p < 0.05) lower in cases compared to the subcohort and these deficits were present across the entire proximal femur. To examine the association of QCT measurements with hip fracture, we merged the two quadrants in the medial and lateral aspects of the FN, IT, and TR. At most sites, QCT measurements were associated significantly (p < 0.001) with hip fracture, the hazard ratio (HR) adjusted for age, body mass index (BMI), and clinical site for a 1‐SD decrease ranged between 2.28 (95% confidence interval [CI], 1.44–3.63) to 6.91 (95% CI, 3.11–15.53). After additional adjustment for total hip (TH) areal BMD (aBMD), trabecular vBMDs at the FN, TR, and TH were still associated with hip fracture significantly (p < 0.001), the HRs ranged from 3.21 (95% CI, 1.65–6.24) for the superolateral FN to 6.20 (95% CI, 2.71–14.18) for medial TR. QCT measurements alone or in combination did not predict fracture significantly (p > 0.05) better than TH aBMD. With an area under the receiver operating characteristic curve (AUC) of 0.901 (95% CI, 0.852–0.950), the regression model combining TH aBMD, age, and trabecular vBMD predicted hip fracture significantly (p < 0.05) better than TH aBMD alone or TH aBMD plus age. These findings confirm that both cortical and trabecular bone contribute to hip fracture risk and highlight trabecular vBMD at the FN and TR as an independent risk factor. © 2012 American Society for Bone and Mineral Research.     

Chronic Kidney Disease Increases the Risk of Hip Fracture: A Prospective Cohort Study in Korean Adults

This study was conducted to examine the association between renal function and hip fracture. We followed up 352,624 Korean adults, who participated in health examinations during 2009–2010 until 2013. Kidney function was assessed by creatinine-based estimated glomerular filtration rate (eGFR) and albuminuria using urine reagent strip results. The incidence of hip fracture was examined by hospital discharge records. Hazard ratios (HRs) for hip fracture were calculated using Cox proportional hazard models after adjusting for multiple confounders. During a mean follow-up of 4.0 years, 1177 participants suffered a hip fracture. Lower eGFR and more severe albuminuria were associated with a higher risk of hip fracture. The HRs for hip fracture were 1.89 (95% confidence interval [CI] 1.47–2.43) and 3.75 (95% CI 2.30–6.11) among participants with eGFRs of 30 to 44 and 15 to 29 mL/min/1.73m² relative to those with an eGFR ≥60 mL/min/1.73m², respectively. The HRs were 1.30 (95% CI 1.02–1.65) for moderate albuminuria and 1.58 (95% CI 1.07–2.35) for severe albuminuria (p for trend = 0.002). Participants with albuminuria had a higher risk of hip fracture than those without albuminuria, even when they belonged to the same eGFR category (HR = 1.75 versus 3.30 for an eGFR of 30 to 44 mL/min/1.73m²; HR = 2.72 versus 7.84 for an eGFR of 15 to 29 mL/min/1.73m²). The effects of each 10 mL/min/1.73m² decrease in eGFR were stronger with advancing albuminuria severity (p_interaction = 0.016). In conclusion, both low eGFR and albuminuria were risk factors for incident hip fracture in Korean adults. Moreover, these factors exerted a synergistic effect on the risk of hip fracture. © 2020 American Society for Bone and Mineral Research.     

BMI and fracture risk in older men: The osteoporotic fractures in men study (MrOS)

Low body mass index (BMI) is a risk factor for fracture, but little is known about the association between high BMI and fracture risk. We evaluated the association between BMI and fracture in the Osteoporotic Fractures in Men Study (MrOS), a cohort of 5995 US men 65 years of age and older. Standardized measures included weight, height, and hip bone mineral density (BMD) by dual‐energy X‐ray absorptiometry (DXA); medical history; lifestyle; and physical performance. Only 6 men (0.1%) were underweight (<18.5 kg/m²); therefore, men in this category were excluded. Also, 27% of men had normal BMI (18.5 to 24.9 kg/m²), 52% were overweight (25 to 29.9 kg/m²), 18% were obese I (30 to 34.9 kg/m²), and 3% were obese II (35 to 39.9 kg/m²). Overall, nonspine fracture incidence was 16.1 per 1000 person‐years, and hip fracture incidence was 3.1 per 1000 person‐years. In age‐, race‐, and BMD‐adjusted models, compared with normal weight, the hazard ratio (HR) for nonspine fracture was 1.04 [95% confidence interval (CI) 0.87–1.25] for overweight, 1.29 (95% CI 1.00–1.67) for obese I, and 1.94 (95% CI 1.25–3.02) for obese II. Associations were weaker and not statistically significant after adjustment for mobility limitations and walking pace (HR = 1.02, 95% CI 0.84–1.23, for overweight; HR = 1.12, 95% CI 0.86–1.46, for obese I, and HR = 1.44, 95% CI 0.90–2.28, for obese II). Obesity is common among older men, and when BMD is held constant, it is associated with an increased risk of fracture. This association is at least partially explained by worse physical function in obese men. © 2011 American Society for Bone and Mineral Research.     

Risk of Subsequent Fractures and Mortality in Elderly Women and Men with Fragility Fractures with and without Osteoporotic Bone Density: The Dubbo Osteoporosis Epidemiology Study

Half of fragility fractures occur in individuals with nonosteoporotic BMD (BMD T‐score > –2.5); however, there is no information on postfracture adverse events of subsequent fracture and mortality for different BMD levels. The objective of this work was to determine the risk and predictors of subsequent fracture and excess mortality following initial fracture according to BMD. The subjects were community‐dwelling participants aged 60+ years from the Dubbo Osteoporosis Epidemiology Study with incident fractures followed from 1989 to 2011. The outcome measurements were as follows: risk of subsequent fracture and mortality according to BMD categorized as normal (T‐score < –1), osteopenia (T‐score ≤ –1 and > –2.5), and osteoporosis (T‐score ≤ –2.5). There were 528 low‐trauma fractures in women and 187 in men. Of these, 12% occurred in individuals with normal BMD (38 women, 50 men) and 42% in individuals with osteopenia (221 women, 76 men). The relative risk (RR) of subsequent fracture was >2.0‐fold for all levels of BMD (normal BMD: 2.0 [1.2 to 3.3] for women and 2.1 [1.2 to 3.8] for men; osteopenia: 2.1 [1.7 to 2.6] for women and 2.5 [1.6 to 4.1] for men; and osteoporosis 3.2 [2.7 to 3.9] for women and 2.1 [1.4 to 3.1] for men. The likelihood of falling and reduced quadriceps strength contributed to subsequent fracture risk in women with normal BMD. By contrast with subsequent fracture risk, postfracture mortality was increased particularly in individuals with low BMD (age‐adjusted standardized mortality ratio [SMR] for osteopenia 1.3 [1.1 to 1.7] and 2.2 [1.7 to 2.9] for women and men, respectively, and osteoporosis 1.7 [1.5 to 2.0] and 2.7 [2.0 to 3.6] for women and men, respectively). This study demonstrates the high burden of subsequent fracture in individuals with normal BMD and osteopenia, and excess mortality particularly for those with osteopenia (and osteoporosis). These findings highlight the importance of these fractures and underscore the gap in evidence for benefit of antiosteoporotic treatment for fragility fracture, in those with only mildly low BMD. © 2014 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     

Proximal femoral density distribution and structure in relation to age and hip fracture risk in women

Hip fracture risk rises exponentially with age, but there is little knowledge about how fracture‐related alterations in hip structure differ from those of aging. We employed computed tomography (CT) imaging to visualize the three‐dimensional (3D) spatial distribution of bone mineral density (BMD) in the hip in relation to age and incident hip fracture. We used intersubject image registration to integrate 3D hip CT images into a statistical atlas comprising women aged 21 to 97 years (n = 349) and a group of women with (n = 74) and without (n = 148) incident hip fracture 4 to 7 years after their imaging session. Voxel‐based morphometry was used to generate Student's t test statistical maps from the atlas, which indicated regions that were significantly associated with age or with incident hip fracture. Scaling factors derived from intersubject image registration were employed as measures of bone size. BMD comparisons of young, middle‐aged, and older American women showed preservation of load‐bearing cortical and trabecular structures with aging, whereas extensive bone loss was observed in other trabecular and cortical regions. In contrast, comparisons of older Icelandic fracture women with age‐matched controls showed that hip fracture was associated with a global cortical bone deficit, including both the superior cortical margin and the load‐bearing inferior cortex. Bone size comparisons showed larger dimensions in older compared to younger American women and in older Icelandic fracture women compared to controls. The results indicate that older Icelandic women who sustain incident hip fracture have a structural phenotype that cannot be described as an accelerated pattern of normal age‐related loss. The fracture‐related cortical deficit noted in this study may provide a biomarker of increased hip fracture risk that may be translatable to dual‐energy X‐ray absorptiometry (DXA) and other clinical images. © 2013 American Society for Bone and Mineral Research.     

A Risk Assessment Tool for Predicting Fragility Fractures and Mortality in the Elderly

Existing fracture risk assessment tools are not designed to predict fracture-associated consequences, possibly contributing to the current undermanagement of fragility fractures worldwide. We aimed to develop a risk assessment tool for predicting the conceptual risk of fragility fractures and its consequences. The study involved 8965 people aged ≥60 years from the Dubbo Osteoporosis Epidemiology Study and the Canadian Multicentre Osteoporosis Study. Incident fracture was identified from X-ray reports and questionnaires, and death was ascertained though contact with a family member or obituary review. We used a multistate model to quantify the effects of the predictors on the transition risks to an initial and subsequent incident fracture and mortality, accounting for their complex interrelationships, confounding effects, and death as a competing risk. There were 2364 initial fractures, 755 subsequent fractures, and 3300 deaths during a median follow-up of 13 years (interquartile range [IQR] 7–15). The prediction model included sex, age, bone mineral density, history of falls within 12 previous months, prior fracture after the age of 50 years, cardiovascular diseases, diabetes mellitus, chronic pulmonary diseases, hypertension, and cancer. The model accurately predicted fragility fractures up to 11 years of follow-up and post-fracture mortality up to 9 years, ranging from 7 years after hip fractures to 15 years after non-hip fractures. For example, a 70-year-old woman with a T-score of −1.5 and without other risk factors would have 10% chance of sustaining a fracture and an 8% risk of dying in 5 years. However, after an initial fracture, her risk of sustaining another fracture or dying doubles to 33%, ranging from 26% after a distal to 42% post hip fracture. A robust statistical technique was used to develop a prediction model for individualization of progression to fracture and its consequences, facilitating informed decision making about risk and thus treatment for individuals with different risk profiles. © 2020 American Society for Bone and Mineral Research.     

Lower fracture risk in older men with higher sclerostin concentration: A prospective analysis from the MINOS study

Sclerostin is synthesized by osteocytes and inhibits bone formation. We measured serum sclerostin levels in 710 men aged 50 years and older. Bone mineral density (BMD) was measured at the lumbar spine, hip, and distal forearm. Serum sclerostin increased with age (unadjusted r = 0.30, p < 0.001). After adjustment for age, weight, and bioavailable 17β‐estradiol, serum sclerostin correlated positively with BMD (r = 0.24 to 0.35, p < 0.001) and negatively with the levels of bone turnover markers (r = ? 0.09 to ? 0.23, p < 0.05 to 0.001). During a 10‐year follow‐up, 75 men sustained fragility fractures. Fracture risk was lower in the two upper quintiles of sclerostin combined versus three lower quintiles combined (6.1 versus 13.5%, p < 0.01). We compared fracture risk in the two highest quintiles combined versus three lower quintiles combined using the Cox model adjusted for age, weight, leisure physical activity, BMD, bone width (tubular bones), prevalent fracture, prevalent falls, ischemic heart disease, and severe abdominal aortic calcification. Men with higher sclerostin concentration had lower fracture risk (adjusted for hip BMD, hazard ratio [HR] = 0.55, 95% confidence interval [CI] 0.31 to 0.96, p < 0.05). The results were similar in 47 men with major fragility fractures (adjusted for lumbar spine BMD: HR = 0.39, 95% CI 0.17 to 0.90, p < 0.05). Men who had higher sclerostin and higher BMD (two highest quintiles) had lower risk of fracture compared with men who had lower BMD and lower sclerostin levels (three lower quintiles) (HR = 0.24, 95% CI 0.10 to 0.62, p < 0.005). Circulating sclerostin was not associated with mortality rate or the incidence of major cardiovascular events. Thus, in older men, higher serum sclerostin levels are associated with lower risk of fracture, higher BMD, and lower bone turnover rate. © 2013 American Society for Bone and Mineral Research.     

Long‐term impact of adherence to oral bisphosphonates on osteoporotic fracture incidence

Adherence to osteoporosis treatments is a critical parameter resulting in suboptimal effectiveness in real‐life practice. The long‐term effect of adherence on fracture risk has not been assessed. This was a retrospective study using provincial health insurance claims databases to assess the association between adherence to oral bisphosphonates (OBP) and incidence of osteoporotic fractures in all Ontario patients with osteoporosis between April 1996 and December 2009. Multivariate logistic regression models were used to assess the association between OBP adherence and fracture risk. Treatment duration was classified into 2‐year intervals. Compliance was estimated with the medication possession ratio (MPR), and persistence was defined as the length of continuous therapy without a gap in refills >30 days. The study cohort was composed of 636,114 patients, among whom 36.1% were prescribed OBPs for 0 to 2 years, 19.7% for 2 to 4 years, 15.1% for 4 to 6 years, 12% for 6 to 8 years, 9.1% for 8 to 10 years, 6.1% for 10to 12 years, and 1.9% for 12 to 14 years. Overall, the mean (SD) compliance for the cohort was 0.72 (0.30) with 53.5% of the patients having compliance >80% and 24.6% being persistent with treatment during the 14‐year follow‐up period. Significant associations between high adherence and reduced fracture risk over the entire 14‐year period were observed; the overall odds ratio for categorical compliance (MPR >80% or MPR ≤80%), continuous compliance, and persistence were 0.909 (95% confidence interval [CI] 0.893–0.925), 0.918 (95% CI 0.893–0.944), and 0.804 (95% CI 0.787–0.821), respectively. In conclusion, adherence to OBP in osteoporosis management is suboptimal in a real‐life setting. A significant positive association exists between poor adherence and increased risk of osteoporotic fractures, which becomes augmented with longer treatment duration. © 2012 American Society for Bone and Mineral Research     

Racial and Ethnic Disparities in Bone Health and Outcomes in the United States

Osteoporosis is a bone disease classified by deterioration of bone microarchitecture and decreased bone strength, thereby increasing subsequent risk of fracture. In the United States, approximately 54 million adults aged 50 years and older have osteoporosis or are at risk due to low bone mass. Osteoporosis has long been viewed as a chronic health condition affecting primarily non-Hispanic white (NHW) women; however, emerging evidence indicates racial and ethnic disparities in bone outcomes and osteoporosis management. The primary objective of this review is to describe disparities in bone mineral density (BMD), prevalence of osteoporosis and fracture, as well as in screening and treatment of osteoporosis among non-Hispanic black (NHB), Hispanic, and Asian adults compared with NHW adults living on the US mainland. The following areas were reviewed: BMD, osteoporosis prevalence, fracture prevalence and incidence, postfracture outcomes, DXA screening, and osteoporosis treatments. Although there are limited studies on bone and fracture outcomes within Asian and Hispanic populations, findings suggest that there are differences in bone outcomes across NHW, NHB, Asian, and Hispanic populations. Further, NHB, Asian, and Hispanic populations may experience suboptimal osteoporosis management and postfracture care, although additional population-based studies are needed. There is also evidence that variation in BMD and osteoporosis exists within major racial and ethnic groups, highlighting the need for research in individual groups by origin or background. Although there is a clear need to prioritize future quantitative and qualitative research in these populations, initial strategies for addressing bone health disparities are discussed. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Impact of Hip Fracture on Mortality: A Cohort Study in Hip Fracture Discordant Identical Twins

Several studies have shown a long‐lasting higher mortality after hip fracture, but the reasons for the excess risk are not well understood. We aimed to determine whether a higher mortality after hip fracture exists when controlling for genetic constitution, shared environment, comorbidity, and lifestyle by use of a nationwide cohort study in hip fracture discordant monozygotic twins. All 286 identical Swedish twin pairs discordant for hip fracture (1972 to 2010) were identified. Comorbidity and lifestyle information was retrieved by registers and questionnaire information. We used intrapair Cox regression to compute multivariable‐adjusted hazard ratios (HRs) for death. During follow‐up, 143 twins with a hip fracture died (50%) compared with 101 twins (35%) without a hip fracture. Through the first year after hip fracture, the rate of death increased fourfold in women (HR = 3.71; 95% confidence interval [CI] 1.32–10.40) and sevenfold in men (HR = 6.67; 95% CI 1.47–30.13). The increased rate in women only persisted during the first year after hip fracture (HR after 1 year = 0.99; 95% CI 0.66–1.50), whereas the corresponding HR in men was 2.58 (95% CI 1.02–6.62). The higher risk in men after the hip fracture event was successively attenuated during follow‐up. After 5 years, the hazard ratio in men with a hip fracture was 1.19 (95% CI 0.29–4.90). On average, the hip fracture contributed to 0.9 years of life lost in women (95% CI 0.06–1.7) and 2.7 years in men (95% CI 1.7–3.7). The potential years of life lost associated with the hip fracture was especially pronounced in older men (>75 years), with an average loss of 47% (95% CI 31–61) of the expected remaining lifetime. We conclude that both women and men display a higher mortality after hip fracture independent of genes, comorbidity, and lifestyle. © 2014 American Society for Bone and Mineral Research.     

Hip fracture and risk of acute myocardial infarction: A nationwide study

Osteoporotic fractures are associated with increased mortality risk. However, little data are available on the risk of acute myocardial infarction (AMI) after hip fracture. Therefore, we investigated whether hip fracture increased the risk of AMI in a large, nationwide cohort study. We obtained data from 8758 patients diagnosed with hip fracture from 2000 to 2009 and from 4 matched controls for each patient from the Longitudinal Health Insurance Database (LHID 2000), Taiwan. Controls were matched for age, sex, comorbid disorders, and enrollment date. All subjects were followed up from the date of enrollment until AMI, death, or the end of data collection (2009). Cox's regression model adjusted for age, sex, comorbid disorders, and medication was used to assess independent factors determining the risk of development of AMI. As expected, despite the matching, the hip fracture patients had more risk factors for AMI at baseline. A total of 8758 subjects with hip fractures and 35,032 controls were identified. Among these patients, 1183 (257 hip fracture patients and 926 controls) developed AMI during the median 3.2‐year (interquartile range 1.4 to 5.8 years) follow‐up period. Patients with hip fractures had a higher incidence of AMI occurrence when compared with controls (8.7/1000 person‐years versus 6.82/1000 person‐years). Multivariate analysis adjusted for baseline covariates indicated that hip fracture was associated with a greater risk for AMI development (hazard ratio [HR] = 1.29; 95% confidence interval [CI] 1.12–1.48; p < 0.001). We conclude that hip fracture is independently associated with a higher risk of subsequent AMI. © 2013 American Society for Bone and Mineral Research     

The Association Between Protein Intake by Source and Osteoporotic Fracture in Older Men: A Prospective Cohort Study

Dietary protein is a potentially modifiable risk factor for fracture. Our objectives were to assess the association of protein intake with incident fracture among older men and whether these associations varied by protein source or by skeletal site. We studied a longitudinal cohort of 5875 men (mean age 73.6 ± 5.9 years) in the Osteoporotic Fractures in Men (MrOS) study. At baseline, protein intake was assessed as percent of total energy intake (TEI) with mean intake from all sources = 16.1%TEI. Incident clinical fractures were confirmed by physician review of medical records. There were 612 major osteoporotic fractures, 806 low‐trauma fractures, 270 hip fractures, 193 spine fractures, and 919 non‐hip non‐spine fractures during 15 years of follow‐up. We used Cox proportional hazards models with age, race, height, clinical site, TEI, physical activity, marital status, osteoporosis, gastrointestinal surgery, smoking, oral corticosteroids use, alcohol consumption, and calcium and vitamin D supplements as covariates to compute hazard ratios (HRs) with 95% confidence intervals (CIs), all expressed per unit (SD = 2.9%TEI) increase. Higher protein intake was associated with a decreased risk of major osteoporotic fracture (HR = 0.92; 95% CI, 0.84 to 1.00) with a similar association found for low‐trauma fracture. The association between protein and fracture varied by protein source; eg, increased dairy protein and non‐dairy animal protein were associated with a decreased risk of hip fracture (HR = 0.80 [95% CI, 0.65 to 0.98] and HR = 0.84 [95% CI, 0.72 to 0.97], respectively), whereas plant‐source protein was not (HR = 0.99 [95% CI, 0.78 to 1.24]). The association between protein and fracture varied by fracture site; total protein was associated with a decreased risk of hip fracture (HR = 0.84 [95% CI, 0.73 to 0.95]), but not clinical spine fracture (HR = 1.06 [95% CI, 0.92 to 1.22]). In conclusion, those with high protein intake (particularly high animal protein intake) as a percentage of TEI have a lower risk of major osteoporotic fracture. © 2016 American Society for Bone and Mineral Research.