Adjustment For Bone Mineral Density Research Articles

Long-term fracture risk in rheumatoid arthritis: impact of early sustained DAS28-remission and restored function, progressive erosive disease, body mass index, autoantibody positivity and glucocorticoids. A cohort study over 10 years

BackgroundRisk of fragility fractures in patients with rheumatoid arthritis (RA) is increased. Disease-related inflammation in RA is associated with low Bone Mineral Density (BMD). However, effects of specific disease factors on fracture occurrence and whether or not such disease effects are independent of BMD are unknown.MethodsAnalysis of fracture outcome in the prospective cohort of 2557 patients with early RA (67% women, mean age 58.1 ± 15.6 years) during an observation period of 10.6 ± 4.7 years. In 602 patients BMD was measured at baseline. The first major fragility fractures were considered. Kaplan-Meier and Cox regression analysis, adjusted for traditional factors, prior fracture, disease activity and period of inclusion, were used to estimate the risk of the outcome.ResultsDuring follow-up fracture occurred in 352 patients (13.8%), a rate of 13/1000 p-y. A proportional risk reduction for the outcome was associated with Body Mass Index (BMI) at baseline, BMI ≥ 30 kg/m2, and over the first two years sustained Disease Activity Score (DAS28)-remission, DAS28-low disease activity and Health Assessment Questionnaire (HAQ) ≤ 0.5. The proportional risk elevation for fractures was associated with BMI ≤ 20 kg/m2, DAS28 at baseline, 6-month and at 1-year, cumulative DAS28 over the two years, RF, erosion score progression at 2-year, HAQ score and HAQ ≥ 1 at 6-month and 1-year and showed a trend for ACPA positivity. The estimated fracture risk was increased in users of glucocorticoids (GC), associated with a higher GC-dosage at follow-ups and a higher cumulative dosage over two years, independently of disease activity. With adjustment for BMD, there was no difference in fracture outcome by exposure to GC. The effects of a higher BMI, DAS28-remission and low HAQ ≤ 0.5 attained at 6-month of treatment initiation and sustained up to 2 years, RF, ACPA, and erosion score progression at 2-year were independent of low BMD.ConclusionsThis analysis supports importance of RA-specific risk factors in early RA for future major fragility fractures. Treat-to-target strategy and restored functional capacity in early RA-disease are important to prevent fractures. Autoantibody positivity, progressively erosive disease, and low weight could have additional value for personalized fracture preventive strategies in early RA.

Prediabetes and Fracture Risk Among Midlife Women in the Study of Women’s Health Across the Nation

Whether prediabetes is associated with fracture is uncertain. To evaluate whether prediabetes before the menopause transition (MT) is associated with incident fracture during and after the MT. This cohort study used data collected between January 6, 1996, and February 28, 2018, in the Study of Women's Health Across the Nation cohort study, an ongoing, US-based, multicenter, longitudinal study of the MT in diverse ambulatory women. The study included 1690 midlife women in premenopause or early perimenopause at study inception (who have since transitioned to postmenopause) who did not have type 2 diabetes before the MT and who did not take bone-beneficial medications before the MT. Start of the MT was defined as the first visit in late perimenopause (or first postmenopausal visit if participants transitioned directly from premenopause or early perimenopause to postmenopause). Mean (SD) follow-up was 12 (6) years. Statistical analysis was conducted from January to May 2022. Proportion of visits before the MT that women had prediabetes (fasting glucose, 100-125 mg/dL [to convert to millimoles per liter, multiply by 0.0555]), with values ranging from 0 (prediabetes at no visits) to 1 (prediabetes at all visits). Time to first fracture after the start of the MT, with censoring at first diagnosis of type 2 diabetes, initiation of bone-beneficial medication, or last follow-up. Cox proportional hazards regression was used to examine the association (before and after adjustment for bone mineral density) of prediabetes before the MT with fracture during the MT and after menopause. This analysis included 1690 women (mean [SD] age, 49.7 [3.1] years; 437 Black women [25.9%], 197 Chinese women [11.7%], 215 Japanese women [12.7%], and 841 White women [49.8%]; mean [SD] body mass index [BMI] at the start of the MT, 27.6 [6.6]). A total of 225 women (13.3%) had prediabetes at 1 or more study visits before the MT, and 1465 women (86.7%) did not have prediabetes before the MT. Of the 225 women with prediabetes, 25 (11.1%) sustained a fracture, while 111 of the 1465 women without prediabetes (7.6%) sustained a fracture. After adjustment for age, BMI, and cigarette use at the start of the MT; fracture before the MT; use of bone-detrimental medications; race and ethnicity; and study site, prediabetes before the MT was associated with more subsequent fractures (hazard ratio for fracture with prediabetes at all vs no pre-MT visits, 2.20 [95% CI, 1.11-4.37]; P = .02). This association was essentially unchanged after controlling for BMD at the start of the MT. This cohort study of midlife women suggests that prediabetes was associated with risk of fracture. Future research should determine whether treating prediabetes reduces fracture risk.

Association between Dairy Product intake and Risk of Osteoporotic Fractures in Postmenopausal Japanese Women: Secondary Analysis of 15-Year Follow-Up data from the Japanese Population-Based Osteoporosis (JPOS) Cohort Study.

Few prospective cohort studies have evaluated the relationship between dairy product intake frequency and risk of osteoporotic fractures in Asians. This study aimed to investigate the association between habitual dairy product intake and risk of osteoporotic fractures. Secondary analysis of prospective cohort study. Five municipalities of Japan. This study included 1,429 postmenopausal Japanese women (age ≥45 years at baseline). Baseline milk-intake frequency was obtained using nurse-administered questionnaires. Intakes of yogurt and cheese, and estimated calcium intake, were assessed using a validated food frequency questionnaire. Osteoporotic fracture was defined as a clinical fracture diagnosed using radiography. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Over a median follow-up period of 15.1 years (interquartile range [IQR], 10.1-15.4 years; total, 18,118 person-years), 172 women sustained at least one osteoporotic fracture. The proportions of participants with milk intakes <1, 1, and ≥2 cups/d were 34.4%, 48.0%, and 17.6%, respectively. After adjustment for age, frequency of yogurt intake, frequency of cheese intake, body mass index, history of osteoporotic fractures, and frequency of natto intake, the HRs compared with that for milk intake <1 cup/d were 0.71 (95% CI: 0.51-0.98) and 0.57 (95% CI: 0.35-0.92) for 1 cup/d and ≥2 cups/d, respectively. After adjustment for bone mineral density, HR significance for milk intakes ≥2 cups/d remained significant. Yogurt and cheese intakes were not related to the risk of osteoporotic fractures. High habitual milk intake, but not a habitual yogurt or cheese intake is associated with a decreased risk of osteoporotic fractures, independent of bone mineral density, in postmenopausal Japanese women.

Menopause-Related Changes in Body Composition Are Associated With Subsequent Bone Mineral Density and Fractures: Study of Women's Health Across the Nation.

During the menopause transition (MT), lean mass decreases and fat mass increases. We examined the associations of these body composition changes during the MT (2 years before to 2 years after the final menstrual period) with bone mineral density (BMD) at the end of the MT and fracture after the MT. We included 539 participants from the Study of Women's Health Across the Nation who were not taking bone-beneficial or bone-detrimental medications before or during the MT. Using multivariable linear regression, we assessed the independent associations of % lean mass loss and % fat mass gain during the MT (mutually adjusted) with femoral neck (FN) and lumbar spine (LS) BMD at the end of the MT, adjusted for pre-MT BMD, pre-MT lean and fat mass, race/ethnicity, Study of Women's Health Across the Nation (SWAN) study site, age, and cigarette use. We used Cox proportional hazards regression to quantify the relations of % lean loss and % fat gain during the MT with fracture after the MT. The Cox model was adjusted for the covariates above plus post-MT use of bone-detrimental medications, and censored at the first use of bone-beneficial medications; we further controlled for FN or LS BMD at the end of the MT. Adjusted for covariates, each standard deviation (SD) (6.9%) increment in lean mass loss was associated with 0.010 g/cm2 lower FN BMD (p < 0.0001); each SD (19.9%) increment in fat mass gain was related to 0.026 g/cm2 greater FN (p=0.009) and LS (p=0.03) BMD. Each SD increment in lean mass loss and fat mass gain was associated with 63% (p=0.001) and 28% (p=0.05) greater fracture hazard after the MT; associations were essentially unchanged by BMD adjustment. MT-related lean mass loss and fat mass gain were associated differentially with BMD; both were independently related to more fractures. Mitigating MT-related body composition changes may reduce fracture risk. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Trabecular bone score and its association with Cobb angle kyphosis in older men: a cross-sectional study for the Osteoporotic Fractures in Men (MrOS) Study.

While vertebral fractures and low bone mineral density (BMD) contribute to kyphosis progression, it is unknown whether the trabecular bone score (TBS) may provide additional information on bone quality that could influence the degree of kyphosis. We hypothesized that degraded TBS would be associated with hyperkyphosis (HK) defined as a Cobb angle > 50°. Using data from 1997 participants of the Osteoporotic Fractures in Men (MrOS) Study who had baseline TBS and Cobb angle kyphosis measured, we investigated whether men with degraded TBS were more likely to be hyperkyphotic, even after adjustment for BMD and prevalent vertebral fractures. Men were an average age of 74 ± 6 (mean ± SD) years with a mean kyphosis angle of 38.6 ± 11.5°, 295 (15%) were classified as hyperkyphotic, and 416 (21%) had degraded TBS. Compared with men with TBS > 1.2, men with degraded TBS were more likely to have HK (OR: 1.47, 95% CI: 1.06-2.06, p = 0.02) after adjusting for age, clinic, race, BMI, hip BMD, and prevalent vertebral fracture. If spine instead of hip BMD was included in the model, the odds ratio decreased to 1.35 (95% CI: 0.97-1.89, p = 0.08). Older men with degraded TBS are more likely to have HK not explained by underlying vertebral fractures.

Characteristics of incidence hip fracture cases in older adults participating in the longitudinal AGES-Reykjavik study.

To examine the relationship between body composition, physical function, and other markers of health with hip fractures in older community-dwelling Icelandic adults. A prospective cohort of 4782 older adults from the AGES-Reykjavik study. Baseline recruitment took place between 2002 and 2006, and information on hip fractures occurring through 2012 was extracted from clinical records. Using multivariate regression analyses, baseline measures of bone health, physical function, and body composition were compared between those who later experienced hip fractures and to those who did not. Associations with the risk of fractures were quantified using Cox regression. Mean age was 76.3 years at baseline. After adjustment for age, regression showed that male hip fracture cases compared with non-cases had (mean (95% confidence interval)) significantly lower thigh muscle cross-sectional area - 5.6 cm2 (- 10.2, - 1.1), poorer leg strength - 28 N (- 49, - 7), and decreased physical function as measured by longer timed up and go test 1.1 s (0.5, 1.7). After adjustment for age, female cases had, compared with non-cases, lower body mass index - 1.5 kg/m2 (- 2.1, - 0.9), less lean mass - 1.6 kg (- 2.5, - 0.8), thigh muscle cross-sectional area - 4.4 cm2 (- 6.5, - 2.3), and worse leg strength - 16 N (- 25, - 6). These differences largely persisted after further adjustment for bone mineral density (BMD), suggesting that body composition may contribute to the risk of fracture independent of bone health. When examining the association between these same factors and hip fractures using Cox regression, the same conclusions were reached. After accounting for age and BMD, older adults who later experienced a hip fracture had poorer baseline measures of physical function and/or body composition, which may at least partly contribute to the risk of falls leading to fracture.

Association between handgrip strength and subsequent vertebral-fracture risk following percutaneous vertebral augmentation.

The aim of this study was to investigate the association between handgrip strength (HGS) and the risk of subsequent vertebral fracture (SVF) after percutaneous vertebral augmentation (PVA). A total of 340 patients aged over 50years with osteoporotic vertebral fracture were enrolled in this 3-year follow-up investigation. HGS was measured with a hand-held dynamometer before PVA. Female patients and male patients were grouped using the HGS threshold recommended by the Asian Working Group for Sarcopenia (AWGS). Kaplan-Meier analysis was used to evaluate SVF-free survival. The hazard ratios (HRs) of HGS for SVF events were estimated with the Cox proportional hazards model. During the follow-up period, a total of 93 patients (27.4%) experienced SVF. Kaplan-Meier analysis showed that the HGS of female patients < 18.0kg and male patients < 28kg was significantly associated with lower SVF-free survival (female patients: p < 0.001, male patients: p = 0.038; log-rank test). Among women, each 1-kg increase in HGS was associated with a 9% lower risk of SVF (HR 0.91, p = 0.035) after adjustment for potential risk factors. Among men, although the associations between low HGS and increased risk of SVF were significant in the crude model (HR 0.79, p < 0.001), this significance disappeared after adjustment for bone mineral density of the femoral neck. Low HGS was significantly associated with lower SVF-free survival among elderly patients who underwent single-level PVA for osteoporotic vertebral fracture.

Low Predictive Value of FRAX Adjusted by Trabecular Bone Score for Osteoporotic Fractures in Korean Women: A Community-Based Cohort Study.

BackgroundThe value of the Fracture Risk Assessment Tool (FRAX) and the trabecular bone score (TBS) for assessing osteoporotic fracture risk has not been fully elucidated in Koreans. We conducted this study to clarify the predictive value of FRAX adjusted by TBS for osteoporotic fractures in Korean women.MethodsAfter screening 7,192 eligible subjects from the Ansung cohort, 1,165 women aged 45 to 76 years with available bone mineral density (BMD) and TBS data were enrolled in this study. We assessed their clinical risk factors for osteoporotic fractures and evaluated the predictive value of FRAX with or without BMD and TBS.ResultsDuring the mean follow-up period of 7.5 years, 99 (8.5%) women suffered major osteoporotic fractures (MOFs) and 28 (2.4%) experienced hip fractures. FRAX without BMD, BMD-adjusted FRAX, and TBS-adjusted FRAX were significantly associated with the risk of MOFs (hazard ratio [HR] per percent increase, 1.08; 95% confidence interval [CI], 1.03 to 1.14; HR, 1.09; 95% CI, 1.03 to 1.15; and HR, 1.07; 95% CI, 1.02 to 1.13, respectively). However, BMD-adjusted FRAX and TBS-adjusted FRAX did not predict MOFs better than FRAX without BMD based on the Harrell’s C statistic. FRAX probabilities showed limited value for predicting hip fractures. The cut-off values of FRAX without BMD, FRAX with BMD, and FRAX with BMD adjusted by TBS for predicting MOFs were 7.2%, 5.0%, and 6.7%, respectively.ConclusionFRAX with BMD and TBS adjustment did not show better predictive value for osteoporotic fractures in this study than FRAX without adjustment. Moreover, the cut-off values of FRAX probabilities for treatment might be lower in Korean women than in other countries.

Feminine-sounding names and electoral performance

Periostin is preferentially expressed by the periosteum, which mainly covers the long bones. Therefore, the role of periostin in osteoporotic fracture (OF) may differ depending on bone type. We performed a case–control study to investigate whether periostin can serve as a predictor of OF risk, particularly after dividing OFs into non-vertebral and vertebral fractures.Among 532 consecutive postmenopausal women not taking any drug or without any disease that could affect bone metabolism, 133 cases with OF (i.e., non-vertebral and/or vertebral fractures) and 133 age- and body mass index-matched controls were enrolled. Non-vertebral (i.e., forearm, humerus, hip, and pelvis; n = 81) and morphological vertebral (n = 62) fractures were identified by an interviewer-assisted questionnaire and lateral thoracolumbar radiographs, respectively. Bone mineral density (BMD) and plasma periostin levels were also measured.Plasma periostin was markedly higher in subjects with non-vertebral fracture than their controls even after adjustment for BMD and potential confounders (P = 0.006). Each standard deviation increment of plasma periostin was associated with a multivariable-adjusted odds ratio of 1.59 for non-vertebral fracture. The odds for non-vertebral fracture were 2.48-fold higher in subjects in the highest periostin tertile compared with those in the lowest periostin tertile (95% confidence interval = 1.10–5.61). However, associations between plasma periostin and vertebral fracture were not observed, regardless of the adjustment model used. Consistently, plasma periostin levels were inversely associated with proximal femur BMD (P = 0.007 to 0.030) but not lumbar spine BMD. In subgroup analyses, plasma periostin had no correlation with the levels of classical bone turnover markers.Plasma periostin may be a potential biomarker of the risk of OF, especially in non-spinal skeletal sites, such as the limbs, rather than spine.

Sex hormone–binding globulin is a biomarker associated with nonvertebral fracture in men on dialysis therapy

Gonadal hormones impact bone health and higher values of sex hormone-binding globulin (SHBG) have been independently associated with fracture risk in men without chronic kidney disease. People with chronic kidney disease have a greatly increased fracture risk, and gonadal dysfunction is common in men receiving dialysis treatment. Nevertheless, in these men the effect of gonadal steroids and SHBG on bone mineral density (BMD) and fracture risk is unknown. Here we investigate relationships between gonadal steroids, SHBG, BMD and fracture in men on long-term dialysis therapy, awaiting kidney or simultaneous pancreas kidney transplantation. Results of serum biochemistry, SHBG, gonadal steroids (total testosterone, calculated free testosterone and estradiol), BMD by dual-energy X-ray absorptiometry and thoracolumbar X-rays were obtained. Multivariable regression models were used to examine associations between SHBG, gonadal steroids, BMD and fracture of 321 men with a mean age of 47 years. Diabetes mellitus was present in 45% and their median dialysis vintage was 24 months. Prior fractures occurred in 42%, 18% had vertebral fracture on lateral spine X-ray, 17% had non-vertebral fragility fracture within 10 years and 7% had both. After adjustment for age, body mass index and dialysis vintage, higher SHBG levels were significantly associated with nonvertebral fractures [odds ratio 1.81 (1.30-2.53)] and remained significant after adjustment for BMD. Calculated free testosterone and estradiol values were not associated with fracture. Prevalent fracture rates were high in relatively young men on dialysis awaiting transplantation. Thus, SHBG is a novel biomarker associated with fracture, which warrants investigation in prospective studies.

A meta-analysis of the association between body mass index and risk of vertebral fracture.

Recent evidence suggests that the relationship between BMI and fracture risk may be site-specific. We conducted a systematic review and meta-analysis of prospective studies to investigate the association between BMI and risk of incident vertebral fracture. PubMed and Embase were searched for relevant articles published from inception through February 15, 2017. Extracted relative risks (RR) from the prospective studies were pooled using random-effects meta-analysis. Six studies were included, with a total of 105,129 participants followed for 3 to 19years. The pooled RR (95% confidence interval [CI]) for vertebral fracture per each standard deviation increase in BMI was 0.94 (95% CI=0.80-1.10) with significant heterogeneity (I 2=88.0%, p<0.001). In subgroup analysis by gender, we found a significant inverse association between BMI and risk of vertebral fracture in men (RR=0.85, 95% CI=0.73-0.98, n=25,617 participants) but not in women (RR=0.98, 95% CI=0.81-1.20, n=79,512 participants). Across studies of women not adjusting for bone mineral density (BMD), there was no significant association between BMI and risk of vertebral fracture (RR=0.91, 95% CI=0.80-1.04, p=0.18, n=72,755 participants). However, BMI was associated with an increased risk of vertebral fracture in studies of women that adjusted for BMD (RR=1.28, 95% CI=1.17-1.40, p<0.001, n=6757 participants). Substantial heterogeneity was found among studies of women (I 2=90.1%, p<0.001), which was partly explained by the adjustment for BMD (adjusted R 2=61%). We found no evidence of publication bias (p=0.40). In conclusion, our findings suggest that there might be gender differences in the relationship of BMI with risk of vertebral fracture. Further research is needed, including the assessment of other measures of adiposity, such as visceral adiposity, on the risk of vertebral fracture.

Abdominal aortic calcification and the risk of bone fractures: a meta-analysis of prospective cohort studies.

The relationship between abdominal aortic calcification (AAC) and bone fracture has been examined by some observational studies, but the results remain discordant. Therefore, we aimed to assess the link between them by conducting a meta-analysis of prospective studies. Relevant studies were identified by searching PubMed and EMBASE databases until the end of December 2016. Summary relative risks (RRs) and 95% confidence intervals (CIs) for associations between AAC and fracture risk were estimated with fixed- or random- effects models. Seven prospective studies were included in the final analysis. The summarized RRs of any type of fractures for the highest compared with the lowest category of AAC were 1.64 (95% CI 1.30-2.07, P=0.000) with mild heterogeneity (I 2=30.1%, P=0.188). Subgroup analysis showed that the association between AAC and fracture was not significantly modified by gender and follow-up length. Risks were similar when analyses were restricted to the studies with adjustment for bone mineral density (BMD) (RR=1.76, 95% CI 1.31-2.38, P=0.000, I 2=49.1%). For the specific type of fracture, severe AAC was significantly related with hip fracture (RR=1.64, 95% CI 1.22-2.20, P=0.001, n=5), but not with vertebral (RR=1.45, 95% CI 0.81-2.58, P=0.213, n=3) or non-vertebral fracture (RR=1.35, 95% CI 0.96-1.88, P=0.081, n=3). There was no evidence of publication bias. Our findings demonstrated that AAC was significantly and independently associated with a higher fracture risk, especially for hip fracture.

Bone density loss on computed tomography at 3-year follow-up in current compared to former male smokers

ObjectivesCigarette smoking negatively affects bone quality and increases fracture risk. Little is known on the effect of smoking cessation and computed tomography (CT)-derived bone mineral density (BMD) decline in the spine. We evaluated the association of current and former smoking with BMD decline after 3-year follow-up. MethodsMale current and former smokers participating in a lung cancer screening trial who underwent baseline and 3-year follow-up CT were included. BMD was measured by manual placement of a region of interest in the first lumbar vertebra and expressed in Hounsfield Unit (HU). Multiple linear regression analysis was used to evaluate the association between pack years smoked and smoking status with BMD decline. Results408 participants were included with median (25th–75th percentile) age of 59.4 (55.9–63.5) years. At the start of the study, 197 (48.3%) participants were current smokers and 211 (51.7%) were former smokers and had a similar amount of pack years. Current smokers had quit smoking for 6 (4–8) years prior to inclusion. There was no difference in BMD between current and former smokers at baseline (109±34 HU vs. 108±32 HU, p=0.96). At 3-year follow-up, current smokers had a mean BMD decline of −3±13 HU (p=0.001), while BMD in former smokers did not change as compared to baseline (1±13 HU, p=0.34). After adjustment for BMD at baseline and body mass index, current smoking was independently associated with BMD decline (−3.8 HU, p=0.003). Age, pack years, and the presence of a fracture at baseline did not associate with BMD decline. ConclusionsCurrent smokers showed a more rapid BMD decline over a 3-year period compared to former smokers. This information might be important to identify subjects at risk for osteoporosis and emphasizes the importance of smoking cessation in light of BMD decline.

Long-term Bone Mineral Density Changes in Antiretroviral-Treated HIV-Infected Individuals.

We compared adjusted bone mineral density (BMD) changes between human immunodeficiency virus (HIV)-infected individuals during the first approximately 7.5 years after antiretroviral therapy (ART) initiation and HIV-uninfected controls. HIV-infected individuals (n = 97) had significantly greater adjusted BMD decline than controls (n = 614) during the first 96 weeks of ART. Subsequently, the rate of BMD decline slowed in HIV-infected individuals but remained greater than the rate of decline in HIV-uninfected individuals at the lumbar spine but not at the hip. In HIV-infected individuals after 96 weeks, no HIV- or treatment-related characteristic was associated with BMD loss, but lower lean body mass was associated with greater BMD loss at both lumbar spine and hip.

Vertebral body morphology is associated with incident lumbar vertebral fracture in postmenopausal women. The OFELY study.

We investigate the predictive role of vertebral anterior cortical curvature and height heterogeneity in the occurrence of vertebral fractures in postmenopausal women. Women who will fracture had shorter vertebral height, greater heterogeneity of height than those who will not fracture, and their anterior vertebral body edge was less concave. Vertebral morphology has been demonstrated to be associated with further risk of fracture. The aim of this study was to analyze vertebral anterior cortical curvature (Ct.curv) and vertebral height heterogeneity in postmenopausal women before the occurrence of a vertebral fracture. This case-control study included 29 postmenopausal women who have underwent incident lumbar vertebral fractures (mean age 71 ± 9years, mean time to fractures 9 ± 4years), age-matched with 57 controls. From lateral X-rays of lumbar spine radiographs (T12 to L4), the following parameters were measured: (1) the posterior, middle, and anterior vertebral heights; (2) the heterogeneity of heights evaluated by the coefficient of variation of these three variables; (3) antero-posterior width, a 2D estimator of cross-sectional area; and (4) Ct.curv. Mean vertebral heights were significantly lower among women who fractured than in controls (p < 0.05). The anterior and middle heights were significantly lower at L4 and L3 levels in fracture group (p = 0.02). The heterogeneity of vertebral height was significantly greater in the fracture group (p = 0.003). In addition, fractured patients had a significantly higher Ct.curv on L3 (p = 0.04). After adjustment for bone mineral density (BMD), only the heterogeneity of vertebral height remained significant (p = 0.005). The current case-control study confirmed the association between vertebral height and occurrence of future vertebral fracture in postmenopausal women. The vertebrae with the smallest Ct.curv tended to fracture less often, and the heterogeneity of vertebral heights was associated with future fracture independently of BMD. An additional validation in a prospective study would be needed to confirm these initial results.

Obésité et ostéoporose

A low body mass index (BMI) is a usual risk factor for fracture. Any decrease of a unit of BMI is associated with a moderate (but significant) decreased risk of fracture. The association is higher for fragility fractures (particularly for hip fractures). However, after adjusting for bone mineral density (BMD), this association is no longer significant. It is now well established that the protective effect of increased weight on the risk of fracture occurs only up to a certain threshold of BMI (25 kg/m2). Beyond that threshold, the incidence of fractures no longer varies. After adjustment for BMD, it seems that a BMI over 30 kg/m2 may be associated with an increased risk of fracture. The publications indicating that obesity is not always protective regarding the occurrence of fractures are recent. The analysis of data (which are otherwise not all unanimous) is complex since the effect of obesity depends on the site of the fracture. In women, obesity seems to be associated with an increased risk of fracture for tibia (upper and lower extremity), femoral shaft and the upper extremity of the humerus. Conversely, obesity appears protective regarding wrist, hip and pelvis fractures. Gender should also be taken into account. For men, obesity (after adjustment for BMD) is a risk factor for hip fracture. For vertebral fractures, obesity would be a protective factor for men but favoring for women. In mechanistic terms, many unknowns remain. Beyond the mechanical stresses, which can be an obvious explanation to understand the increased incidence of certain fractures in obese; the complexity of adipose tissue should also be taken into account. This endocrine organ has in fact substantial metabolic properties. It is especially capable of secreting adipokines. The best known of these is leptin. Leptin (measured in the serum) has a protective effect on bone. Another adipokine, adiponectin, may also be involved in bone metabolism with an opposite action compared to leptin. In addition, obesity belongs to the category of disorders causing low level of inflammation. Thus, secretion by adipose tissue of pro-inflammatory cytokines could also be an interesting explanatory track.

Plasma periostin associates significantly with non-vertebral but not vertebral fractures in postmenopausal women: Clinical evidence for the different effects of periostin depending on the skeletal site

BackgroundPeriostin is preferentially expressed by the periosteum, which mainly covers the long bones. Therefore, the role of periostin in osteoporotic fracture (OF) may differ depending on bone type. We performed a case–control study to investigate whether periostin can serve as a predictor of OF risk, particularly after dividing OFs into non-vertebral and vertebral fractures. MethodsAmong 532 consecutive postmenopausal women not taking any drug or without any disease that could affect bone metabolism, 133 cases with OF (i.e., non-vertebral and/or vertebral fractures) and 133 age- and body mass index-matched controls were enrolled. Non-vertebral (i.e., forearm, humerus, hip, and pelvis; n=81) and morphological vertebral (n=62) fractures were identified by an interviewer-assisted questionnaire and lateral thoracolumbar radiographs, respectively. Bone mineral density (BMD) and plasma periostin levels were also measured. ResultsPlasma periostin was markedly higher in subjects with non-vertebral fracture than their controls even after adjustment for BMD and potential confounders (P=0.006). Each standard deviation increment of plasma periostin was associated with a multivariable-adjusted odds ratio of 1.59 for non-vertebral fracture. The odds for non-vertebral fracture were 2.48-fold higher in subjects in the highest periostin tertile compared with those in the lowest periostin tertile (95% confidence interval=1.10–5.61). However, associations between plasma periostin and vertebral fracture were not observed, regardless of the adjustment model used. Consistently, plasma periostin levels were inversely associated with proximal femur BMD (P=0.007 to 0.030) but not lumbar spine BMD. In subgroup analyses, plasma periostin had no correlation with the levels of classical bone turnover markers. ConclusionsPlasma periostin may be a potential biomarker of the risk of OF, especially in non-spinal skeletal sites, such as the limbs, rather than spine.

Wrist Fracture and Risk of Subsequent Fracture: Findings from the Women's Health Initiative Study.

Wrist fractures are common in postmenopausal women and are associated with functional decline. Fracture patterns after wrist fracture are unclear. The goal of this study was to determine the frequency and types of fractures that occur after a wrist fracture among postmenopausal women. We carried out a post hoc analysis of data from the Women's Health Initiative Observational Study and Clinical Trials (1993-2010) carried out at 40 US clinical centers. Participants were postmenopausal women aged 50 to 79 years at baseline. Mean follow-up duration was 11.8 years. Main measures included incident wrist, clinical spine, humerus, upper extremity, lower extremity, hip, and total non-wrist fractures and bone mineral density (BMD) in a subset. Among women who experienced wrist fracture, 15.5% subsequently experienced non-wrist fracture. The hazard for non-wrist fractures was higher among women who had experienced previous wrist fracture than among women who had not experienced wrist fracture: non-wrist fracture overall (hazard ratio [HR] = 1.40, 95% confidence interval [CI] 1.33-1.48), spine (HR = 1.48, 95% CI 1.32-1.66), humerus (HR = 1.78, 95% CI 1.57-2.02), upper extremity (non-wrist) (HR = 1.88, 95% CI 1.70-2.07), lower extremity (non-hip) (HR = 1.36, 95% CI 1.26-1.48), and hip (HR = 1.50, 95% CI 1.32-1.71) fracture. Associations persisted after adjustment for BMD, physical activity, and other risk factors. Risk of non-wrist fracture was higher in women who were younger when they experienced wrist fracture (interaction p value 0.02). Associations between incident wrist fracture and subsequent non-wrist fracture did not vary by baseline BMD category (normal, low bone density, osteoporosis). A wrist fracture is associated with increased risk of subsequent hip, vertebral, upper extremity, and lower extremity fractures. There may be substantial missed opportunity for intervention in the large number of women who present with wrist fractures.

Associations of 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D With Bone Mineral Density, Bone Mineral Density Change, and Incident Nonvertebral Fracture.

Relationships between 1,25-dihydroxyvitamin D (1,25(OH)2 D) and skeletal outcomes are uncertain. We examined the associations of 1,25(OH)2 D with bone mineral density (BMD), BMD change, and incident non-vertebral fractures in a cohort of older men and compared them with those of 25-hydroxyvitamin D (25OHD). The study population included 1000 men (aged 74.6 ± 6.2 years) in the Osteoporotic Fractures in Men (MrOS) study, of which 537 men had longitudinal dual-energy X-ray absorptiometry (DXA) data (4.5 years of follow-up). A case-cohort design and Cox proportional hazards models were used to test the association between vitamin D metabolite levels and incident nonvertebral and hip fractures. Linear regression models were used to estimate the association between vitamin D measures and baseline BMD and BMD change. Interactions between 25OHD and 1,25(OH)2 D were tested for each outcome. Over an average follow-up of 5.1 years, 432 men experienced incident nonvertebral fractures, including 81 hip fractures. Higher 25OHD was associated with higher baseline BMD, slower BMD loss, and lower hip fracture risk. Conversely, men with higher 1,25(OH)2 D had lower baseline BMD. 1,25(OH)2 D was not associated with BMD loss or nonvertebral fracture. Compared with higher levels of calcitriol, the risk of hip fracture was higher in men with the lowest 1,25(OH)2 D levels (8.70 to 51.60 pg/mL) after adjustment for baseline hip BMD (hazard ratio [HR] = 1.99, 95% confidence interval [CI] 1.19-3.33). Adjustment of 1,25(OH)2 D data for 25OHD (and vice versa) had little effect on the associations observed but did attenuate the hip fracture association of both vitamin D metabolites. In older men, higher 1,25(OH)2 D was associated with lower baseline BMD but was not related to the rate of bone loss or nonvertebral fracture risk. However, with BMD adjustment, a protective association for hip fracture was found with higher 1,25(OH)2 D. The associations of 25OHD with skeletal outcomes were generally stronger than those for 1,25(OH)2 D. These results do not support the hypothesis that measures of 1,25(OH)2 D improve the ability to predict adverse skeletal outcomes when 25OHD measures are available. © 2015 American Society for Bone and Mineral Research.

High-sensitivity C-reactive protein is an independent risk factor for non-vertebral fractures in women and men: The Tromsø Study

Low-grade inflammation is associated with fractures, while the relationship between inflammation and bone mineral density (BMD) is less clear. Moreover, any gender differences in the sensitivity to inflammation are still poorly elucidated. We therefore tested the hypothesis that high-sensitivity C-reactive protein (CRP) is an independent risk factor for low BMD and non-vertebral fractures, in both genders, and whether there are gender differences in these associations.CRP levels and BMD at the total hip and femoral neck were measured in 1902 women and 1648 men between 55 and 74years of age, at baseline in the Tromsø Study, Norway, in 2001–2002. Non-vertebral fractures were registered from hospital X-ray archives during an average of 7.2years follow-up. Linear regression analyses were used for CRP association with BMD and Cox proportional hazards model for fracture prediction by CRP.During 25 595 person-years follow-up, 366 (19%) women and 126 (8%) men suffered a non-vertebral fracture. There was no association between CRP and BMD in women, but an inverse association in men (p=0.001) after adjustment for age and body mass index. Each standard deviation (SD) increase in log-CRP was associated with an increased risk for non-vertebral fracture by 13% in women and 22% in men (hazard ratios (HRs) 1.13, 95% confidence interval (CI) 1.02–1.26, p=0.026 and 1.22, 95% CI=1.00–1.48, p=0.046, respectively). After adjustment for BMD and other risk factors, women with CRP in the upper tertile exhibited 39% higher risk for fracture than those in the lowest tertile of CRP (HR=1.39, 95% CI=1.06–1.83, p=0.017), while men in the upper tertile exhibited 80% higher risk (HR=1.80, 95% CI=1.10–2.94, p=0.019).In summary, CRP was not associated with BMD in women but inversely associated in men, and predicted fractures in both genders. We infer that inflammation influence fracture risk in both women and men, although the biological mechanisms may differ between the genders.