Jesper Ryg

Hip Fracture Patients at Risk of Second Hip Fracture: A Nationwide Population-Based Cohort Study of 169,145 Cases During 1977–2001†‡

In patients with prior hip fracture (HFx), little is known about time frame and risk factors of second HFx, as well as the ensuing mortality. The aim of the study was to elucidate the incidence of second HFx and subsequent mortality. All 169,145 patients with a first HFx in Denmark during 1977–2001 were followed for up to 25 yr and compared with the background population. Data on fractures, vital status, comorbidity, redeemed prescriptions, and socio‐demographic variables were retrieved from national registers. Median follow‐up was 3.8 yr, corresponding to 1,041,177 patient‐years. A total of 27,834 patients had a second HFx. The cumulative incidence was 9% after 1 yr and 20% after 5 yr, being significantly higher than expected (2% and 12%, respectively; p < 0.05). The RR of second HFx was 2.2 (95% CI: 2.0–2.5) at 1 yr and did not normalize until 15 yr (RR = 1.01, 95% CI: 1.0–1.02). Risk factors for a second HFx were female sex (HR = 1.36, 95% CI: 1.32–1.40), age (HR = 1.68, 95% CI: 1.60–1.76 in patients >85 yr), alcoholism (HR = 1.61, 95% CI: 1.51–1.72), any prior fracture (HR = 1.08, 95%CI :1.04–1.11), and living alone (HR = 1.06, 95% CI: 1.04–1.09). Both sexes had higher mortality at 1 and 5 yr after a second HFx compared with the background population (men—1 yr: 27% versus 9%, p < 0.05; 5 yr: 64% versus 40%, p < 0.05; women—1 yr: 21% versus 10%, p < 0.05; 5 yr: 58% versus 41%, p < 0.05). Patients with HFx are at 2‐fold risk of further HFx and the subsequent mortality is highly increased. We propose that programs for secondary prevention should be developed and tested.

Femur ultrasound (FemUS)—first clinical results on hip fracture discrimination and estimation of femoral BMD

SummaryA quantitative ultrasound (QUS) device for measurements at the proximal femur was developed and tested in vivo (Femur Ultrasound Scanner, FemUS). Hip fracture discrimination was as good as for DXA, and a high correlation with hip BMD was achieved. Our results show promise for enhanced QUS-based assessment of osteoporosis.IntroductionDual X-ray absorptiometry (DXA) at the femur is the best predictor of hip fractures, better than DXA measurements at other sites. Calcaneal quantitative ultrasound (QUS) can be used to estimate the general osteoporotic fracture risk, but no femoral QUS measurement has been introduced yet. We developed a QUS scanner for measurements at the femur (Femur Ultrasound Scanner, FemUS) and tested its in vivo performance.MethodsUsing the FemUS device, we obtained femoral QUS and DXA on 32 women with recent hip fractures and 30 controls. Fracture discrimination and the correlation with femur bone mineral density (BMD) were assessed.ResultsHip fracture discrimination using the FemUS device was at least as good as with hip DXA and calcaneal QUS. Significant correlations with total hip bone mineral density were found with a correlation coefficient R2 up to 0.72 and a residual error of about one half of a T-score in BMD.ConclusionsQUS measurements at the proximal femur are feasible and show a good performance for hip fracture discrimination. Given the promising results, this laboratory prototype should be reengineered to a clinical applicable instrument. Our results show promise for further enhancement of QUS-based assessment of osteoporosis.

Functional level at admission is a predictor of survival in older patients admitted to an acute geriatric unit

BackgroundFunctional decline is associated with increased risk of mortality in geriatric patients. Assessment of activities of daily living (ADL) with the Barthel Index (BI) at admission was studied as a predictor of survival in older patients admitted to an acute geriatric unit.MethodsAll first admissions of patients with age >65 years between January 1st 2005 and December 31st 2009 were included. Data on BI, sex, age, and discharge diagnoses were retrieved from the hospital patient administrative system, and data on survival until September 6th 2010 were retrieved from the Civil Personal Registry. Co-morbidity was measured with Charlson Co-morbidity Index (CCI). Patients were followed until death or end of study.Results5,087 patients were included, 1,852 (36.4%) men and 3,235 (63.6%) women with mean age 81.8 (6.8) and 83.9 (7.0) years respectively. The median [IQR] length of stay was 8 days, the median follow up [IQR] 1.4 [0.3; 2.8] years and in hospital mortality 8.2%. Mortality was greater in men than in women with median survival (95%-CI) 1.3 (1.2 -1.5) years and 2.2 (2.1-2.4) years respectively (p < 0.001). The median survivals (95%-CI) stratified on BI groups in men (n = 1,653) and women (n = 2,874) respectively were: BI 80-100: 2.6 (1.9-3.1) years and 4.5 (3.9-5.4) years; BI 50-79: 1.7 (1.5-2.1) years and 3.1 (2.7-3.5) years; BI 25-49: 1.5 (1.3-1.9) years and 1.9 (1.5-2.2) years and BI 0-24: 0.5 (0.3-0.7) years and 0.8 (0.6-0.9) years. In multivariate logistic regression analysis with BI 80-100 as baseline and controlling for significant covariates (sex, age, CCI, and diseases of cancer, haematology, cardiovascular, respiratory, infectious and bone and connective tissues) the odds ratios for 3 and 12 months survival (95%-CI) decreased with declining BI: BI 50-79: 0.74 (0.55-0.99) (p < 0.05) and 0,80 (0.65-0.97)(p < 0.05); BI 25-49: 0.44 (0.33-0.59)(p < 0.001) and 0.55 (0.45-0.68)(p < 0.001); and BI 0-24: 0.18 (0.14-0.24)(p < 0.001) and 0.29 (0.24-0.35)(p < 0.001) respectively.ConclusionBI is a strong independent predictor of survival in older patients admitted to an acute geriatric unit. These data suggest that assessment of ADL may have a potential role in decision making for the clinical management of frail geriatric inpatients.

Central nervous system medications and falls risk in men aged 60–75 years: the Study on Male Osteoporosis and Aging (SOMA)

INTRODUCTION drugs acting on the central nervous system (CNS) increase falls risk. Most data on CNS drugs and falls are in women/mixed-sex populations. This study assessed the relationship between CNS drugs and falls in men aged 60-75 years. METHODS a questionnaire was sent to randomly selected Danish men aged 60-75 years. Cross-sectional data on CNS drugs and falls in the previous year were available for 4,696 men. Logistic regression investigated the relationship between falls and CNS drugs. RESULTS the median age was 66.3 (IQR = 63.1-70.0) years; 21.7% were fallers. The following were associated with fallers (OR; 95% CI): opiates (2.4; 1.5-3.7), other analgesics (1.7; 1.4-2.1), antiepileptics (2.8; 1.5-5.1), antidepressants (2.8; 1.9-4.1) and anxiolytics/hypnotics (1.5; 0.9-2.6). Effects of opiates interacted strongly and significantly with age, with a marked association with falls in the older half of the subjects only. No significant associations were found between antipsychotics and fallers. Selective serotonin reuptake inhibitors and tricyclics were significantly associated with fallers (3.1; 2.0-5.0 and 2.2; 1.0-4.7, respectively). CONCLUSION several CNS drug classes are associated with an approximately 2-3-fold increase risk of falls in men aged 60-75 years randomly selected from the population. Further longitudinal data are now required to confirm and further investigate the role of CNS drugs in falls causation in men.

Danish register-based study on the association between specific cardiovascular drugs and fragility fractures

Objective To determine whether drugs used in treatment of cardiovascular diseases (CVD-drugs), including hypertension, increase the risk of fragility fractures in individuals above the age of 65 years. Design Retrospective nationwide cohort study. Setting Danish nationwide national registers. Participants All individuals in Denmark ≥65 years who used specified CVD-drugs in the study period between 1999 and 2012. Main outcomes measures Time-dependent exposure to CVD-drugs (nitrates, digoxin, thiazides, furosemide, ACE inhibitors, angiotensin receptor antagonists, β-blockers, calcium antagonists and statins) was determined by prescription claims from pharmacies. The association between use of specific CVD-drugs and fragility fractures was assessed using multivariable Poisson regression models, and adjusted incidence rate ratios (IRRs) were calculated. Results Overall, 1 586 554 persons were included, of these 16.1% experienced a fall-related fracture. The multivariable Poisson regression analysis showed positive associations between fracture and treatment with furosemide, thiazide and digoxin. IRRs during the first 14 days of treatment were for furosemide IRR 1.74 (95% CI 1.61 to 1.89) and for thiazides IRR 1.41 (1.28 to 1.55); IRR during the first 30 days of treatment with digoxin was 1.18 (1.02 to 1.37). Conclusions Use of furosemide, thiazides and digoxin was associated with elevated rates of fragility fractures among elderly individuals. This may warrant consideration when considering diuretic treatment of hypertension in elderly individuals.

Radiographic Absorptiometry as a Screening Tool in Male Osteoporosis: Results from the Odense Androgen Study

Background: Osteoporosis screening with dual-energy absorptiometry (DXA) is not recommended due to low diagnostic utility and costs. Radiographic absorptiometry (RA) determines bone mineral density (BMD) of the phalangeal bones of the hand and is a potential osteoporosis pre-screening tool. Purpose: To determine the ability of RA to identify patients with osteoporosis in a male population. Material and Methods: As part of the Odense Androgen Study, we measured BMD of the intermediate phalanges of the second to fourth finger, lumbar spine (L2–L4), and total hip in 218 men aged 60–74 years (mean 68.8 years), randomly invited from the population, using RA (MetriScan) and DXA (Hologic 4500-A). Osteopenia and osteoporosis were defined as a T-score of less than −1.0 and -2.5, respectively, in the hip and/or lumbar spine. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were computed. Results: BMDRA of the phalanges correlated significantly with BMDDXA of the hip (R=0.47, P<0.001) and lumbar spine (R=0.46, P<0.001). A total of 105 men (48.2%) were osteopenic and 15 (6.9%) osteoporotic. The AUC (SE) value for detecting osteoporosis was 0.75 (0.06). The sensitivity and specificity of RA in identifying osteoporosis were 0.93 and 0.50, respectively. Conclusion: BMDRA correlated weakly with BMDDXA of the lumbar spine and total hip, and RA has a moderate ability to identify osteoporotic individuals. Nevertheless, RA may be used as a pre-screening tool in men, since the diagnosis may be ruled out in half the population at little cost.

Novel Use of the Nintendo Wii Board for Measuring Isometric Lower Limb Strength: A Reproducible and Valid Method in Older Adults.

Background Portable, low-cost, objective and reproducible assessment of muscle strength in the lower limbs is important as it allows clinicians to precisly track progression of patients undergoing rehabilitation. The Nintendo Wii Balance Board (WBB) is portable, inexpensive, durable, available worldwide, and may serve the above function. Objective The purpose of the study was to evaluate (1) reproducibility and (2) concurrent validity of the WBB for measuring isometric muscle strength in the lower limb. Methods A custom hardware and software was developed to utilize the WBB for assessment of isometric muscle strength. Thirty older adults (69.0±4.2 years of age) were studied on two separate occasions on both the WBB and a stationary isometric dynamometer (SID). On each occasion, three recordings were obtained from each device. For the first recording, means and maximum values were used for further analysis. The test-retest reproducibility was examined using intraclass correlation coefficients (ICC), Standard Error of Measurement (SEM), and limits of agreement (LOA). Bland-Altman plots (BAP) and ICC’s were used to explore concurrent validity. Results No systematic difference between test-retest was detected for the WBB. ICC within-device were between 0.90 and 0.96 and between-devices were from 0.80 to 0.84. SEM ranged for the WBB from 9.7 to 13.9%, and for the SID from 11.9 to 13.1%. LOA ranged for the WBB from 20.3 to 28.7% and for the SID from 24.2 to 26.6%. The BAP showed no relationship between the difference and the mean. Conclusions A high relative and an acceptable absolute reproducibility combined with a good validity was found for the novel method using the WBB for measuring isometric lower limb strength in older adults. Further research using the WBB for assessing lower limb strength should be conducted in different study-populations.

Low bone mineral density is not related to failure in femoral neck fracture patients treated with internal fixation

Background and purpose — Internal fixation (IF) in femoral neck fractures has high reoperation rates and some predictors of failure are known, such as age, quality of reduction, and implant positioning. Finding new predictors of failure is an ongoing process, and in this study we evaluated the importance of low bone mineral density (BMD). Patients and methods — 140 consecutive patients (105 females, median age 80) treated with IF had a dual-energy X-ray absorptiometry (DXA) scan of the hip performed median 80 days after treatment. The patients’ radiographs were evaluated for fracture displacement, implant positioning, and quality of reduction. From a questionnaire completed during admission, 2 variables for comorbidity and walking disability were chosen. Primary outcome was low hip BMD (amount of mineral matter per square centimeter of hip bone) compared to hip failure (resection, arthroplasty, or new hip fracture). A stratified Cox regression model on fracture displacement was applied and adjusted for age, sex, quality of reduction, implant positioning, comorbidity, and walking disability. Results — 49 patients had a T-score below –2.5 (standard deviation from the young normal reference mean) and 70 patients had a failure. The failure rate after 2 years was 22% (95% CI: 12–39) for the undisplaced fractures and 66% (CI: 56–76) for the displaced fractures. Cox regression showed no association between low hip BMD and failure. For the covariates, only implant positioning showed an association with failure. Interpretation — We found no statistically significant association between low hip BMD and fixation failure in femoral neck fracture patients treated with IF.

Cancer incidence in persons with elevated cobalamin levels

Elevated cobalamin level (ECL) is an epiphenomenon for several cancer types. The clinical significance of ECL at routine testing is, however, unknown. The aim of this study was to examine cancer incidences among persons with ECL.

Estimation of femoral bone density from trabecular direct wave and cortical guided wave ultrasound velocities measured at the proximal femur in vivo

Bone mineral density (BMD) of the proximal femur is a predictor of hip fracture risk. We developed a Quantitative Ultrasound (QUS) scanner for measurements at this site with similar performance (FemUS). In this study we tested if ultrasound velocities of direct waves through trabecular bone and of guided waves through cortical bone could be used to estimate BMD. In two centres, Kiel and Odense, we measured time‐of‐flight (TOF) of waves through the trabecular greater trochanter and cortical intertrochanter as well as a wave through soft tissue only. TOF was adjusted for leg width using ultrasound echoes reflected from the skin of the leg to yield speed‐of‐sound (SOS) of different wave components. Data were cross‐calibrated and pooled (62 women). Bivariate correlations and a multivariate model were calculated for the estimation of femur BMD. BMD correlated both with trabecular and cortical SOS but not soft tissue SOS. Coefficient of determination, percentage residual error (RMSE) and level of significance (p) were R2=0.51, RMSE=12.6%, p<0.0001 for trabecular and R2=0.53, RMSE=12.3%, p<0.0001 for cortical measurements. The combination of trabecular, cortical and soft tissue SOS improved the correlation to R2=0.69, RMSE=10.4%, p<0.0001. Multiwave ultrasound methods allow estimation of femoral BMD with a low residual error.