Sister’s fracture history may be associated with perimenopausal bone fragility and modifies the predictability of fracture risk

Summary  The present study investigated the effects of first degree relatives’ fractures on fracture incidence after the menopause. Sister’s, but not other relatives’, wrist or hip fracture history was associated with increased risk of fragility fractures after the menopause. This suggests genetic predisposition to bone fragility among postmenopausal women. Objective  The aim of the present study was to investigate the association between first degree relatives’ fractures and perimenopausal bone fragility. Materials and methods  The study sample of 971 perimenopausal women was extracted from randomly selected Kuopio Osteoporosis Risk Factor and Prevention cohort and measured with dual X-ray absorptiometry in femoral neck (FN) in baseline (1989–1991), in 5 years (1994–97), and in 10 years (1999–2001). All low-trauma energy fractures during the 10-year follow-up were recorded based on self-reports and validated from medical records. First degree relatives’ history of life-time hip and wrist fractures (exact classification or trauma energy not specified) was questioned by postal inquiries. Results  There was a significant correlation between fathers’ vs. brothers’ and mothers’ vs. sisters’ fractures (p < 0.01 in Pearson bivariate correlations). Sister’s, but not mother’s, father’s, or brother’s wrist and hip fractures were associated with significantly lowered 10-year fragility fracture-free survival rate (HR = 0.56, p = 0.006). Sisters’ or other relatives’ fractures were not associated with FN bone loss rate or bone mineral density (BMD) in the follow-up measurements (p = NS in ANCOVA). The predictive power of BMD for fragility fractures differed according to sisters’ fracture history: Baseline FN T score predicted fracture-free survival only among women without sisters’ fracture history (HR 0.62, p < 0.001 vs. women with sisters’ fracture in Cox regression). Conclusions  In conclusion, sisters’ fracture history is associated with 10-year fracture-free survival in perimenopausal women but not with BMD or its changes. Predictability of fragility fracture risk with BMD may depend on sister’s fracture history. This may indirectly suggest genetic predisposition to bone fragility independently of BMD.     

Association of Grip Strength Change with Menopausal Bone Loss and Related Fractures: A Population-Based Follow-Up Study

The aim of the present study was to investigate the association between grip strength change and bone health according to menopausal status. A random sample of 971 pre- to postmenopausal women from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study cohort was measured with dual X-ray absorptiometry in the lumbar spine (LS) and femoral neck (FN) and grip strength with pneumatic squeeze dynamometer at baseline (1989–1991), 5 years (1994–1997), and 10 years (1999–2001). Fractures were recorded based on self-reports and validated from medical records. Women were divided into two groups according to change in grip strength quartile from baseline to 5-year follow-up: not improved (n = 735) and improved (n = 236). In the total population, the greatest bone loss was observed in perimenopausal (beginning of menopause during follow-up, n = 311) women [P < 0.001 vs. premenopausal women (n = 139)], and it declined in postmenopausal (n = 521) women [P < 0.001 by analysis of covariance (ANCOVA)]. The perimenopausal bone loss rate was significantly lower in women in the improved group in comparison to the not improved group (P < 0.01) in contrast to the pre- and postmenopausal groups (P > 0.05). Accordingly, there was a greater decline in perimenopausal LS and FN T-scores in the improved group vs. the not improved group over the first 5-year follow-up interval (P < 0.05 by ANCOVA) and remained unchanged over the 10-year follow-up. In perimenopausal women, there was a trend toward higher fracture-free survival rate in the improved group (82%) vs. the not improved group (88%) after 10 years. Adjustments did not change the results. In conclusion, maintenance of grip strength is associated with menopausal bone loss and future fractures.     

When should densitometry be repeated in healthy peri- and postmenopausal women: the Danish osteoporosis prevention study.

Intervention should be considered in postmenopausal women with bone mineral density (BMD) > or = 1 SD below the reference (T or Z score < -1). However, it is unclear when densitometry should be repeated. This study aimed at determining the need for repeat DXA within 5 years in untreated peri-/postmenopausal women to detect declines of T or Z score to below -1 with 85% confidence. A cohort of 925 healthy women (aged 51.2 +/- 2.9 years) were followed within the Danish Osteoporosis Prevention Study (DOPS) for 5 years without hormone-replacement therapy (HRT). DXA of spine, hip, and forearm was done at 0,1, 2, 3, and 5 years (Hologic QDR-1000/2000). The annual loss in SD units was 0.12 +/- 0.10 at the spine (1.3%), 0.10 +/- 0.09 at the femoral neck (1.2%), and 0.07 +/- 0.09 at the ultradistal (UD) forearm (1.0%). Accordingly, T scores below -1 developed earlier at the spine. The need for a future DXA scan to predict declines of T and Z scores below -1 depended strongly on baseline BMD. In subjects with a positive T score, the risk of developing T < -1 remained at <15% for 5 years at all measured sites. A new scan was needed after 1 year if the T score was below -0.5, and after 3 years if the T score was between 0 and -0.5. Slightly longer intervals apply if Z scores are used. Follow-up densitometry in untreated women should be individually targeted from baseline BMD rather than scheduled at fixed time intervals. An algorithm for planning repeat densitometry in perimenopausal women is provided.     

Bone mineral density and risk factors for osteoporosis—A population-based study of 1600 perimenopausal women

Population-based epidemiological studies on osteoporosis are few. Our study evaluated the effects of menopause and certain putative behavioral risk factors on bone mineral density (BMD). Spinal and femoral neck BMD were measured with dual X-ray absorptiometry (DXA) from 1600 perimenopausal women aged 48–59 years (mean 53.2 years) with no diseases or medications known to affect bone metabolism. These women were a selected sample of the Kuopio Osteoporosis Risk Factor and Prevention Study population (n=14,220). There was a wide variation of BMD among perimenopausal women. Menopause had a major effect on BMD. Postmenopausal women had significantly lower BMD in both spine (-6.2%) and femoral neck (-3.9%) as compared with premenopausal women. Multiple regression analysis showed that weight, menopausal status, age, and grip strength were significant independent predictors of both spinal and femoral BMD. Additionally, physical activity was found to be a significant predictor of femoral BMD, and alcohol consumption was a significant predictor of spinal BMD. However, current anthropometric and lifestyle factors explained only 18.7–25.4% of the variability of BMD. Therefore, the estimation of the risk factor status at menopause is not an adequate substitute for bone densitometry. However, our results may in part help clinicians to identify the risk groups at which to direct bone density measurements.     

The Associations of Dietary Inflammatory Potential With Musculoskeletal Health in Chinese Community-Dwelling Older People: The Mr. OS and Ms. OS (Hong Kong) Cohort Study

Inflammation, an important contributory factor of muscle and bone aging, is potentially modulated by diet. This study examined the associations of dietary inflammatory index (DII) score with musculoskeletal parameters and related disease outcomes in 3995 community-dwelling Chinese men and women aged ≥65 years in Hong Kong. DII score at baseline was estimated from a food frequency questionnaire. Bone mineral density (BMD) and muscle mass estimated by dual-energy X-ray absorptiometry (DXA), hand grip strength, gait speed, and chair stand test were measured at baseline, year 4, and year 14. The associations of DII score with the longitudinal changes of musculoskeletal parameters, and incidence of osteoporosis, sarcopenia, and fractures were examined by using general linear model, multinomial logistic regression model, and Cox proportional hazards regression model, respectively. After multiple adjustments, each tertile increase in DII score in men was associated with 0.37 (95% confidence interval [CI], 0.10–0.64) kg loss in grip strength and 0.02 (95% CI, 0.01–0.03) m/s loss in gait speed over 4 years. In men, the highest tertile of DII was associated with a higher risk of incident fractures, with adjusted and competing death adjusted hazard ratio (HR) (95% CI) of 1.56 (1.14–2.14) and 1.40 (1.02–1.91), respectively. In women, DII score was not significantly associated with any muscle-related outcomes or incidence of fracture, but a significant association between higher DII score and risk of osteoporosis at year 14 was observed, with the highest tertile of DII score having adjusted odds ratio (OR) (95% CI) of 1.90 (1.03–3.52). In conclusion, pro-inflammatory diet consumption promoted loss of muscle strength and physical function, and increased risk of fractures in older Chinese men. Pro-inflammatory diets had no significant association with muscle related outcomes but increased the long-term risk of osteoporosis in older Chinese women. © 2022 American Society for Bone and Mineral Research (ASBMR).     

Bisphosphonates and bone fractures in long-term kidney transplant recipients

BACKGROUND: There is little information on the role of bisphosphonates and bone mineral density (BMD) measurements for the follow-up and management of bone loss and fractures in long-term kidney transplant recipients. METHODS: To address this question, we retrospectively studied 554 patients who had two BMD measurements after the first year posttransplant and compared outcomes in patients treated, or not with bisphosphonates between the two BMD assessments. Kaplan-Meier survival and stepwise Cox regression analyses were performed to examine fracture-free survival rates and the risk-factors associated with fractures. RESULTS: The average time (+/-SE) between transplant and the first BMD was 1.2+/-0.05 years. The time interval between the two BMD measurements was 2.5+/-0.05 years. There were 239 and 315 patients in the no-bisphosphonate and bisphosphonate groups, respectively. Treatment was associated with significant preservation of bone loss at the femoral neck (HR 1.56, 95% CI 1.21-2.06, P=0.0007). However, there was no association between bone loss at the femoral neck and fractures regardless of bisphosphonate therapy. Stepwise Cox regression analyses showed that type-1 diabetes, baseline femoral neck T-score, interleukin-2 receptor blockade, and proteinuria (HR 2.02, 0.69, 0.4, 1.23 respectively, P<0.01), but not bisphosphonates, were associated with the risk of fracture. CONCLUSIONS: Bisphosphonates may prevent bone loss in long-term kidney transplant recipients. However, these data suggest a limited role for the initiation of therapy after the first posttransplant year to prevent fractures.     

Effect of Total Hip Bone Area on Osteoporosis Diagnosis and Fractures

DXA is affected by skeletal size, with smaller bones giving lower areal BMD despite equal material density. Whether this size effect confounds the use of BMD as a diagnostic and fracture risk assessment tool is unclear. We identified 16,205 women of white ethnicity ≥50 yr of age undergoing baseline hip assessment with DXA (1998–2002) from a population‐based database that contains all clinical DXA test results for the Province of Manitoba, Canada. Total hip measurements were categorized according to quartile in total hip bone area (Q1 = smallest, Q4 = largest). Longitudinal health service records were assessed for the presence of nontraumatic osteoporotic fracture codes during a mean of 3.2 yr of follow‐up after BMD testing (757 osteoporotic fractures, 186 hip fractures). Total hip bone area strongly affected osteoporosis diagnosis with much higher rates in Q1 (14.4%) than Q4 (8.9%). However, incident fracture rates were constant across all area quartiles, and prevalent fractures were paradoxically fewer in smaller area quartiles (p < 0.001 for trend). Age was a potential confounder that correlated positively with area (r = 0.12, p < 0.0001). When age was not included in a Cox regression model, Q1 seemed to have a lower rate of incident osteoporotic fractures (HR = 0.80, 95% CI = 0.66–0.98, reference Q4) and hip fractures (HR = 0.63, 95% CI = 0.43–0.94) for a given level of BMD. In age‐adjusted regression models, total hip BMD was strongly predictive of incident osteoporotic fractures (HR per SD = 1.83, 95% CI = 1.68–1.99) and hip fractures (HR per SD = 2.80, 95% CI = 2.33–3.35), but there was no independent effect of bone area (categorical or continuous). Nested matched subgroup analysis and ROC analysis confirmed that bone area had no appreciable effect on incident fractures. We conclude that total hip areal BMD categorizes a substantially higher fraction of women with smaller bone area as being osteoporotic despite younger age. Incident fracture rates correlate equally well with BMD across all bone area quartiles when adjusted for age.     

Association of Bone Density Monitoring in Routine Clinical Practice With Anti-Osteoporosis Medication Use and Incident Fractures: A Matched Cohort Study

Routine bone mineral density (BMD) monitoring of individuals during the initial 5 years of anti-osteoporosis treatment is controversial. Using a registry-based cohort from the Province of Manitoba, Canada, we compared anti-osteoporosis medication use and fracture outcomes in women with versus without BMD monitoring receiving anti-osteoporosis medication. We identified 4559 women aged 40 years and older receiving anti-osteoporosis therapy with serial BMD testing (monitoring) within 5 years (mean interval 3.2 years) and 4559 propensity score–matched women without BMD monitoring. We assessed anti-osteoporosis medication use over 5 years from a population-based retail pharmacy database. Incident fractures to 10 years from health services data. During median 10 years observation, 1225 (13.4%) women developed major osteoporotic fracture, including 382 (4.2%) with hip fractures. Monitored women had significantly better fracture-free survival for major osteoporotic fracture (p = 0.040; 10-year cumulative risk 1.9% lower, 95% confidence interval [CI] 0.3–3.6%) and hip fracture ( p = 0.001; 10-year cumulative risk 1.8% lower, 95% CI 0.7–2.8%) compared with women who were not monitored. Hazard ratios (HRs) were significantly lower in monitored versus not monitored women for major osteoporotic fracture (HR = 0.89, 95% CI 0.80–0.98) and hip fracture (HR = 0.74, 95% CI 0.63–0.87). Days of medication use, medication persistence ratio, and treatment switching over 5 years were greater in monitored versus not monitored women. At the end of 5 years, more women in the monitored group persisted on treatment and more switched treatment, with switching behavior associated with an observed interval reduction in BMD. In conclusion, our findings suggest a possible role for BMD monitoring after initiating anti-osteoporosis therapy in the routine clinical practice setting. © 2019 American Society for Bone and Mineral Research.     

Bone mineral density at menopause does not predict breast cancer incidence

In this prospective study in 2,137 perimenopausal and early postmenopausal women who were followed over a 13.1-year period of time, we observed no association between bone mineral density measured at the beginning of menopause and the subsequent risk of breast cancer. INTRODUCTION: This study aimed to investigate the relationship between BMD and the risk of breast cancer (BC) in young postmenopausal women. METHODS: As part of a clinical research program, 2,137 women who were perimenopausal or within their 5 first postmenopausal years were scanned between 1988-1990 and reviewed on average 13.1 years after their initial examination. Ninety-eight incident BC cases were recorded throughout the follow-up. RESULTS: Women with incident BC significantly differed from those who had never had BC with regard to age at menarche, age of birth of 1st child, familial history of BC and postmenopausal hormone therapy (PHT) use. There was no significant difference between the two groups for baseline DXA of the spine. There was a trend for BC cases for having lower femoral neck BMD compared to women without BC. However, women with low BMD were more likely to have taken PHT by the end of the study. In Cox multivariate analyses the relationship between BC risk and femoral neck BMD no longer existed. CONCLUSIONS: There was no relationship between BMD measured within the first postmenopausal years and the risk of BC, which makes unlikely the possibility of using BMD as a predictor factor for BC in early postmenopausal women.     

Prediction of clinical non-spine fractures in older black and white men and women with volumetric BMD of the spine and areal BMD of the hip: the Health, Aging, and Body Composition Study*.

In a prospective study of 1446 black and white adults 70-79 yr of age (average follow-up, 6.4 yr), vertebral TrvBMD from QCT predicted non-spine fracture in black and white women and black men, but it was not a stronger predictor than total hip aBMD from DXA. Hip aBMD predicted non-spine fracture in black men. INTRODUCTION: Areal BMD (aBMD) at multiple skeletal sites predicts clinical non-spine fractures in white and black women and white men. The predictive ability of vertebral trabecular volumetric BMD (TrvBMD) for all types of clinical non-spine fractures has never been tested or compared with hip aBMD. Also, the predictive accuracy of hip aBMD has never been tested prospectively for black men. MATERIALS AND METHODS: We measured vertebral TrvBMD with QCT and hip aBMD with DXA in 1446 elderly black and white adults (70-79 yr) in the Health, Aging, and Body Composition Study. One hundred fifty-two clinical non-spine fractures were confirmed during an average of 6.4 yr of >95% complete follow-up. We used Cox proportional hazards regression to determine the hazard ratio (HR) and 95% CIs of non-spine fracture per SD reduction in hip aBMD and vertebral TrvBMD. RESULTS: Vertebral TrvBMD and hip aBMD were both associated with risk of non-spine fracture in black and white women and black men. The age-adjusted HR of fracture per SD decrease in BMD was highest in black men (hip aBMD: HR = 2.04, 95% CI = 1.03, 4.04; vertebral TrvBMD: HR = 3.00, 95% CI = 1.29, 7.00) and lowest in white men (hip aBMD: HR = 1.23, 95% CI = 0.85, 1.78; vertebral TrvBMD: HR = 1.06, 95% CI = 0.73, 1.54). Adjusted for age, sex, and race, each SD decrease in hip aBMD was associated with a 1.67-fold (95% CI = 1.36, 2.07) greater risk of fracture, and each SD decrease in vertebral TrvBMD was associated with a 1.47-fold (95% CI = 1.18, 1.82) greater risk. Combining measurements of hip aBMD and vertebral TrvBMD did not improve fracture prediction. CONCLUSIONS: Low BMD measured by either spine QCT or hip DXA predicts non-spine fracture in older black and white women and black men. Vertebral TrvBMD is not a stronger predictor than hip aBMD of non-spine fracture.     

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

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

Low Vitamin D Status Is Associated With Impaired Bone Quality and Increased Risk of Fracture-Related Hospitalization in Older Australian Women

The vitamin D debate relates in part to ideal public health population levels of circulating 25-hydroxyvitamin D (25OHD) to maintain bone structure and reduce fracture. In a secondary analysis of 1348 women aged 70 to 85 years at baseline (1998) from the Perth Longitudinal Study of Aging in Women (a 5-year calcium supplementation trial followed by two 5-year extensions), we examined the dose-response relations of baseline plasma 25OHD with hip DXA BMD at year 1, lumbar spine BMD, and trabecular bone score (TBS) at year 5, and fracture-related hospitalizations over 14.5 years obtained by health record linkage. Mean baseline plasma 25OHD was 66.9 ± 28.2 nmol/L and 28.5%, 36.4%, and 35.1% of women had levels <50, 50 to 74.9, and ≥75 nmol/L, respectively. Generalized additive models showed that total hip and femoral neck BMD and TBS, but not spine BMD, were higher with increasing plasma 25OHD up to 100 nmol/L. Compared with those with 25OHD <50 nmol/L, women with 25OHD ≥75 nmol/L had significantly higher total hip and femoral neck BMD at year 1 (3.3% to 3.9%) and TBS at year 5 (2.0%), all P < 0.05. During the follow-up, 27.6% of women experienced any fracture-related hospitalization and 10.6% hip fracture-related hospitalization. Penalized spline regression models showed a decrease in risk with increased 25OHD levels up to 65 nmol/L and 75 nmol/L for hip fracture and any fracture-related hospitalization, respectively. Cox regression grouped analyses showed that compared with women with 25OHD <50 nmol/L, those with 25OHD levels 50 to 74.9 and ≥75 nmol/L had significantly lower risk for hip fracture [HR 0.60 (95% CI, 0.40 to 0.91) and 0.61 (95% CI, 0.40 to 0.92), respectively], and any fracture-related hospitalization [HR 0.77 (95% CI, 0.59 to 0.99) and 0.70 (95% CI, 0.54 to 0.91), respectively]. In older white women, 25OHD levels >50 nmol/L are a minimum public health target and 25OHD levels beyond 75 nmol/L may not have additional benefit to reduce fracture risk. © 2019 American Society for Bone and Mineral Research.     

Effect of enzyme replacement therapy with imiglucerase on BMD in type 1 Gaucher disease.

The effect of ERT with imiglucerase on BMD in type 1 GD was studied using BMD data from the International Collaborative Gaucher Group Gaucher Registry. Data were analyzed for 160 untreated patients and 342 ERT-treated patients. Imiglucerase significantly improves BMD in patients with GD, with 8 years of ERT leading to normal BMD. INTRODUCTION: The objective was to determine the effect of enzyme replacement therapy (ERT; Cerezyme, imiglucerase) on BMD in type 1 Gaucher disease (GD). MATERIALS AND METHODS: The study population included all adults (men, 18-70 years; women, 18-50 years) enrolled in the International Collaborative Gaucher Group (ICGG) Gaucher Registry for whom lumbar spine BMD measurements were available. BMD data with up to 8 years of follow-up were analyzed for 160 patients who received no ERT and 342 patients treated with ERT alone. BMD was assessed by DXA of the lumbar spine. Z scores for patients with GD were compared with a reference population. From the model's estimate, percent of patients by age and sex with osteoporosis (T score < or = -2.5) were calculated. RESULTS: DXA Z scores for patients with GD in the no ERT (untreated) group were significantly below normal (y intercept = -0.80 Z score units, p < 0.001) and remained approximately 1 SD below the reference population over time (slope = -0.010 Z score units per year, p = 0.68). The DXA Z scores for patients with GD who received ERT at a dose of 60 U/kg/2 weeks were significantly lower than the reference population at baseline (y-intercept = -1.17 Z score units, p < 0.001), but improved significantly over time (slope = +0.132 Z score units per year, p < 0.001). A significant dose-response relationship was noted for the ERT group, with the slopes for the three main dosing groups of 15, 30, and 60 U/kg/2 weeks of +0.064, +0.086, and +0.132 Z score units per year, respectively. The BMD of patients with GD treated with ERT increased to -0.12 (60 U/kg/2 weeks), -0.48 (30 U/kg/2 weeks), and -0.66 (15 U/kg/2 weeks) SD of the mean of the reference population after 8 years of ERT, approaching the reference population. Estimated risk of osteoporosis of this GD population, if left untreated, ranged from approximately 10 to 30% in women and 10% to 25% in men. CONCLUSIONS: ERT with imiglucerase (Cerezyme) may increase BMD in patients with GD. Response to treatment with imiglucerase is slower for BMD than for hematologic and visceral aspects of GD. A normal (age- and sex-adjusted) BMD should be a therapeutic goal for patients with type 1 GD.     

Pleiotropic Effects of Obesity on Fracture Risk: The Study of Women's Health Across the Nation

Some aspects of an obese body habitus may protect against fracture risk (higher bone mineral density [BMD] and greater tissue padding), while others may augment that risk (greater impact forces during a fall). To examine these competing pathways, we analyzed data from a multisite, multiethnic cohort of 1924 women, premenopausal or early perimenopausal at baseline. Obesity was defined as baseline body mass index (BMI) > 30 kg/m². Composite indices of femoral neck strength relative to fall impact forces were constructed from DXA‐derived bone size, BMD and body size. Incident fractures were ascertained annually during a median follow‐up of 9 years. In multivariable linear regression adjusted for covariates, higher BMI was associated with higher BMD but with lower composite strength indices, suggesting that although BMD increases with greater skeletal loading, the increase is not sufficient to compensate for the increase in fall impact forces. During the follow‐up, 201 women had fractures. In Cox proportional hazard analyses, obesity was associated with increased fracture hazard adjusted for BMD, consistent with greater fall impact forces in obese individuals. Adjusted for composite indices of femoral neck strength relative to fall impact forces, obesity was associated with decreased fracture hazard, consistent with a protective effect of soft tissue padding. Further adjustment for hip circumference, a surrogate marker of soft tissue padding, attenuated the obesity–fracture association. Our findings support that there are at least three major mechanisms by which obesity influences fracture risk: increased BMD in response to greater skeletal loading, increased impact forces, and greater absorption of impact forces by soft tissue padding. © 2014 American Society for Bone and Mineral Research.     

Ten-year absolute risk of osteoporotic fractures according to BMD T score at menopause: the Danish Osteoporosis Prevention Study.

In the non-HRT arms of the DOPS study, 10-year fracture risk was higher at each level of T score than predicted by the Kanis algorithm. Under-reporting of fractures in registers and inclusion of HRT users are probable explanations for inappropriately low fracture risk estimates for younger women. INTRODUCTION: International recommendations highlight the importance of absolute fracture risk in establishing intervention thresholds. The available estimates of long-term risk have been derived by combining relative risks from meta-analyses with U.S. normative BMD data and Swedish fracture incidence records. We validated the 2001 Kanis risk algorithm using incident fractures observed in untreated women in the first 10 years of the Danish Osteoporosis Prevention Study (DOPS). Comparisons were also made with the relative risks derived from a recent meta-analysis of 12 cohort studies. MATERIALS AND METHODS: We analyzed DXA of the spine and hip from 872 women who were enrolled in the non-hormone replacement therapy (HRT) arms of the study and had not received HRT, bisphosphonates, or raloxifene. We collected verified reports of fractures at each visit. We focused on fractures of the hip, spine, shoulder, and forearm to provide risks comparable with the Kanis algorithm. Accordingly, asymptomatic radiographic vertebral fractures were not included. RESULTS: Seventy-eight women (9%) sustained relevant fractures. The risk of fracture increased by 1.32 (95% CI, 1.02; 1.70) for each unit decrease in femoral neck T score and by 1.30 (95% CI, 1.06; 1.58) for each unit decrease in lumbar spine T score at baseline. Absolute fracture risk was higher than expected from the Kanis algorithm at all T score levels. The difference was greatest for participants in the higher range of T scores. At T = -1, the observed risk was 10.9% as opposed to an expected risk of 5.7%. Relative risk gradients were similar to those of the recent meta-analysis. CONCLUSIONS: In healthy women, examined in the first year or two after menopause, 10-year fracture risk was higher at each level of BMD T score than expected from the model by Kanis et al. Inclusion of HRT users in the cohorts used may have led to higher BMD values and lower absolute fracture risk in the Kanis model. These longitudinal data can be used directly in estimating absolute fracture risk in untreated north European women from BMD at menopause.     

Number of osteoporotic sites and fracture risk assessment: a cohort study from the Manitoba Bone Density Program.

Site-discordance in BMD assessment is common and significantly affects patient categorization. Greater number of osteoporotic sites correlates with lower T scores at each index site. This largely explains the positive association between number of osteoporotic sites and fracture risk. INTRODUCTION: Site-discordance in BMD is common when used to classify patients based on a cut-off T score of -2.5. It is unclear whether fracture risk assessment is improved by considering BMD information from multiple sites. Our objective was to assess the contribution of number of osteoporotic sites to overall fracture risk. MATERIALS AND METHODS: The study population was drawn from the regionally based clinical database of the Manitoba Bone Density Program that includes all clinical DXA test results for the Province of Manitoba, Canada. Analyses were limited to 16,505 women>or=50 years of age at the time of baseline DXA of the spine (L1-L4) and hip (three sites). During follow-up (3.2+/-1.5 years), longitudinal health service records showed 765 women with at least one osteoporotic fracture code (hip, forearm, spine, or humerus). RESULTS: Of 5012 women classified as osteoporotic by at least one site (T score -2.5 or lower), almost one half (2370; 47%) were abnormal at only a single site. Among the 1856 women with an osteoporotic total hip measurement, mean total hip T scores decreased as the number of additional osteoporotic sites increased (-2.58, no other osteoporotic sites; -2.69, one other site; -2.87, two other sites; -3.17, three other sites; Spearman r=-0.44, p<0.0001). Age-adjusted fracture risk from a Cox proportional hazards model increased as the number of osteoporotic sites increased (p<0.0001), but number of osteoporotic sites was no longer an independent predictor after total hip BMD was included as a covariate (p=0.19). Covariate adjustment for other sites of BMD measurement attenuated, but did not eliminate, the effect of number of osteoporotic sites. CONCLUSIONS: Site-discordance is common and significantly affects patient categorization when different skeletal sites are used for diagnosis. Greater number of osteoporotic sites correlates with lower T scores at each index site. This largely explains the positive association between number of osteoporotic sites and fracture risk.     

Low Grip Strength is a Strong Risk Factor of Osteoporosis in Postmenopausal Women

Objective

To investigate the effect of grip strength on bone mineral density (BMD) in postmenopausal women. Low BMD is related to risk of fracture and falling is the strongest factor for fragility fractures. Handgrip strength is a reliable indicator of muscle strength and muscle strength is associated with falling.

Methods

For the present study 120 women were divided into two groups: those ≤65 years and those >65 years. Serum 25 hydroxyvitamin D (25OHD), BMD, and handgrip strength were measured to observe the effect of age on 25OHD, grip strength, and BMD, as well as the effect of 25OHD on grip strength and BMD. The correlation between grip strength and BMD was investigated.

Results

In the 120 patients, 25OHD was 24.31 ± 8.29 ng/mL. There were 37 cases with 25OHD <20 ng/mL and 83 cases with 25 OHD ≥20 ng/mL. The patients with 25OHD <20 ng/mL had significantly lower femoral neck BMD, most of them with a T score ≤?2.5 (P < 0.05). BMD measurement showed 66 patients with femoral neck T ≤?2.5, 30 cases with total hip T ≤?2.5 and 90 cases with lumbar BMD T ≤?2.5. The maximum grip strength in the group is 22.28 ± 6.17 kg. There were 38 cases with the maximum grip strength <20 kg and 82 cases with the maximum grip strength ≥20 kg. Patients >65 years had lower 25OHD, lower maximum grip strength, and lower BMD. The osteoporosis risk in postmenopausal women with a maximum grip strength <20 kg and who were >65 years was significantly elevated.

Conclusion

Handgrip strength and 25OHD decrease with aging in postmenopausal women. The patients with lower 25OHD level had significantly lower BMD of femoral neck. The patients with lower handgrip strength had significantly lower BMD of lumbar spine, femoral neck, and total hip. Grip strength measurement is the simplest muscle strength measurement method. Our study confirmed that low grip strength was correlated with low BMD and was a strong risk factor for osteoporosis in postmenopausal women.

     

Identification of osteopenic women at high risk of fracture: the OFELY study.

About one-half of women with incident fractures have BMD above the WHO diagnostic threshold of osteoporosis. In the OFELY study, low BMD, increased markers of bone turnover, and prior fracture could be used to identify, within osteopenic women, those at high risk of fracture. INTRODUCTION: Recent data suggest that about one-half of women with incident fractures have BMD above the World Health Organization (WHO) diagnostic threshold of osteoporosis (T score相似文献   

Muscle Strength and Body Composition Are Clinical Indicators of Osteoporosis

We examined the role of muscle strength, lean tissue distribution, and overall body composition as indicators of osteoporosis (OP) in a pooled sample of 979 Finnish postmenopausal women (mean age 68.1 years) from the Kuopio Osteoporosis Risk Factor and Prevention study. Bone mineral density (BMD) at the femoral neck (FN) and total body composition were assessed by dual-energy X-ray absorptiometry scans. The women (n = 979) were divided into three groups according to WHO criteria, based on FN BMD T score: normal (n = 474), osteopenia (n = 468), and OP (n = 37). Soft tissue proportions, fat mass index (FMI, fat/height2), lean mass index (LMI, lean/height2), and appendicular skeletal muscle mass (ASM, (arms + legs)/height2) were calculated. Handgrip and knee extension strength measurements were made. OP subjects had significantly smaller LMI (p = 0.001), ASM (p = 0.001), grip strength (p < 0.0001), and knee extension strength (p < 0.05) but not FMI (p > 0.05) compared to other subjects. Grip and knee extension strength were 19 and 16 % weaker in OP women compared to others, respectively. The area under the receiver operating characteristic curve was 69 % for grip and 71 % for knee extension strength. In tissue proportions only LMI showed predictive power (63 %, p = 0.016). An overall linear association of LMI (R2 = 0.007, p = 0.01) and FMI (R2 = 0.028, p < 0.001) with FN BMD remained significant. In the multivariate model, after adjusting for age, grip strength, leg extension strength, FMI, LMI, number of medications, alcohol consumption, current smoking, dietary calcium intake, and hormone therapy, grip strength (adjusted OR = 0.899, 95 % CI 0.84-0.97, p < 0.01), leg extension strength (OR = 0.998, 95 % CI 0.99-1, p < 0.05), and years of hormone therapy (OR = 0.905, 95 % CI 0.82-1, p < 0.05) remained as significant determinants of OP. Muscle strength tests, especially grip strength, serve as an independent and useful tool for postmenopausal OP risk assessment. In addition, lean mass contributes to OP in this age group. Muscle strength and lean mass should be considered separately since both are independently associated with postmenopausal BMD.     

Grade 1 Vertebral Fractures Identified by Densitometric Lateral Spine Imaging Predict Incident Major Osteoporotic Fracture Independently of Clinical Risk Factors and Bone Mineral Density in Older Women

Because prevalent vertebral fracture (VF) is a strong predictor of future fractures, they are important to identify in clinical practice as osteoporosis medications are effective and can be used to reduce fracture risk in postmenopausal women with VF. Lateral spine imaging (LSI) with dual-energy X-ray absorptiometry (DXA) can be used to diagnose VFs accurately but is not widespread in clinical practice. The prognostic value of grade 1 (20% to 25% compression) VFs diagnosed by LSI with DXA has been insufficiently studied. The aim of this study was to determine if grade 1 VF is associated with incident fracture in older women. Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures (SUPERB) is a population-based study of 3028 older women from Gothenburg, Sweden. Included women were 75 to 80 years of age at baseline, answered questionnaires, and were scanned with DXA (Discovery A, Hologic, Waltham, MA, USA). LSI was used to diagnose VFs, which were classified using the Genant semiquantitative method. Cox regression models were used to estimate the association between VFs at baseline and X-ray–verified incident fractures, with adjustment for confounders. Women with a grade 1 VF (n = 264) or a grade 2–3 VF (n = 349) were compared with women without any fracture (n = 1482). During 3.6 years (median, interquartile range [IQR] 1.5 years) of follow-up, 260 women had any incident fracture and 213 a major osteoporotic fracture (MOF). Women with only grade 1 VF had increased risk of any fracture (hazard ratio [HR] = 1.67; 95% confidence interval [CI] 1.18–2.36) and MOF (HR = 1.86; 95% CI 1.28–2.72). For MOF, this association remained after adjustment for clinical risk factors and femoral neck bone mineral density (BMD). In conclusion, grade 1 VFs were associated with incident MOF, also after adjustment for clinical risk factors and BMD, indicating that all VF identified by DXA should be considered in the evaluation of fracture risk in older women. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research..