Summary
The Risk-stratified Osteoporosis Strategy Evaluation (ROSE) study investigated the effectiveness of a two-step screening program for osteoporosis in women. We found no overall reduction in ...fractures from systematic screening compared to the current case-finding strategy. The group of moderate- to high-risk women, who accepted the invitation to DXA, seemed to benefit from the program.
Introduction
The purpose of the ROSE study was to investigate the effectiveness of a two-step population-based osteoporosis screening program using the Fracture Risk Assessment Tool (FRAX) derived from a self-administered questionnaire to select women for DXA scan. After the scanning, standard osteoporosis management according to Danish national guidelines was followed.
Methods
Participants were randomized to either screening or control group, and randomization was stratified according to age and area of residence. Inclusion took place from February 2010 to November 2011. Participants received a self-administered questionnaire, and women in the screening group with a FRAX score ≥ 15% (major osteoporotic fractures) were invited to a DXA scan. Primary outcome was incident clinical fractures. Intention-to-treat analysis and two per-protocol analyses were performed.
Results
A total of 3416 fractures were observed during a median follow-up of 5 years. No significant differences were found in the intention-to-treat analyses with 34,229 women included aged 65–80 years. The per-protocol analyses showed a risk reduction in the group that underwent DXA scanning compared to women in the control group with a FRAX ≥ 15%, in regard to major osteoporotic fractures, hip fractures, and all fractures. The risk reduction was most pronounced for hip fractures (adjusted SHR 0.741,
p
= 0.007).
Conclusions
Compared to an office-based case-finding strategy, the two-step systematic screening strategy had no overall effect on fracture incidence. The two-step strategy seemed, however, to be beneficial in the group of women who were identified by FRAX as moderate- or high-risk patients and complied with DXA.
.
Objectives. To determine if patients receiving oral bisphosphonates are at excess risk of atrial fibrillation (AF), stroke and myocardial infarction.
Design. Register‐based restricted cohort ...study.
Setting. National Hospital Discharge Register and National Prescriptions Database (1995–2005).
Subjects. Fracture patients beginning bisphosphonates (n = 15 795) were matched with unexposed fracture patients of the same age, sex and fracture type (n = 31 590).
Results. Incidence rates of AF were 16.5/1000 person years in untreated fracture patients and 20.6/1000 person years in bisphosphonate users. An age‐ and sex‐adjusted hazard ratio (HR) of 1.29 (1.17–1.41) was found for probable AF by Cox proportional hazards analysis. The effect size was reduced to HR of 1.18 (1.08–1.29) by adjustment for co‐medications and comorbidity. Selective prescribing was suggested by the observation that (i) risks were increased even in patients who stopped therapy after the first packet and (ii) risks were not increased by high adherence. Bisphosphonate‐exposed patients were at increased risk of hospital‐treated AF adjusted HR: 1.13 (1.01–1.26), but the risk amongst bisphosphonate users was inversely proportional to adherence. There was no increased risk of ischaemic stroke and an increased risk of myocardial infarction was not significant after adjustment for comorbidity.
Conclusions. The increased occurrence of AF in fracture patients who are users of oral bisphosphonates should be attributed to targeting of bisphosphonates to patients who are already at increased risk of cardiovascular events.
Summary
Population-based screening for osteoporosis is still controversial and has not been implemented. Non-participation in systematic screening was evaluated in 34,229 women age 65–81 years. ...Although participation rate was high, non-participation was associated with comorbidity, aging other risk factors for fractures, and markers of low social status, e.g., low income, pension, and living alone. A range of strategies is needed to increase participation, including development of targeted information and further research to better understand the barriers and enablers in screening for osteoporosis.
Introduction
Participation is crucial to the success of a screening program. The objective of this study was to analyze non-participation in Risk-stratified Osteoporosis Strategy Evaluation, a two-step population-based screening program for osteoporosis.
Methods
Thirty-four thousand two hundred twenty-nine women aged 65 to 81 years were randomly selected from the background population and randomized to either a screening group (intervention) or a control group. All women received a self-administered questionnaire designed to allow calculation of future risk of fracture based on FRAX. In the intervention group, women with an estimated high risk of future fracture were invited to DXA scanning. Information on individual socioeconomic status and comorbidity was obtained from national registers.
Results
A completed questionnaire was returned by 20,905 (61%) women. Non-completion was associated with older age, living alone, lower education, lower income, and higher comorbidity. In the intervention group, ticking “not interested in DXA” in the questionnaire was associated with older age, living alone, and low self-perceived fracture risk. Women with previous fracture or history of parental hip fracture were more likely to accept screening by DXA. Dropping out when offered DXA, was associated with older age, current smoking, higher alcohol consumption, and physical impairment.
Conclusions
Barriers to population-based screening for osteoporosis appear to be both psychosocial and physical in nature. Women who decline are older, have lower self-perceived fracture risk, and more often live alone compared to women who accept the program. Dropping out after primary acceptance is associated not only with aging and physical impairment but also with current smoking and alcohol consumption. Measures to increase program participation could include targeted information and reducing physical barriers for attending screening procedures.
Summary
Context
Ageing in men is associated with changes in levels of sex hormones.
Objective
To evaluate differences in sex hormones in young and elderly men and the significance of comorbidity and ...fat mass on sex hormones in elderly men.
Design
Cross‐sectional.
Patients
Seven hundred and eighty‐three men aged 20–29 years and 600 men aged 60–74 years randomly recruited from the background population.
Measurements
Sex hormones and sex hormone‐binding globulin (SHBG) were measured, and reference intervals were determined in healthy individuals in both groups and in elderly men stratified according to whether they were obese or lean (waist circumference ≥102 cm).
Results
Sex hormones were lower and SHBG higher in elderly men compared with the young cohort. Lower cut‐offs for total testosterone (TT) in healthy, young and elderly men were similar Lower cut‐off (95% CI): Young: 11·7 (11·2–12·1) vs elderly: 11·2 (10·3–12·1) nmol/l, but lower and higher cut‐offs of bioavailable testosterone (BT) and free testosterone (FT) were higher in young men. Higher levels of androgens were found in healthy elderly men compared with those with a chronic disease or obesity. Androgens were inversely associated with central fat mass (CFM), whereas SHBG was inversely and directly associated with CFM and lower extremity fat mass, respectively, in both young and elderly men.
Conclusion
Reference intervals for TT were comparable in healthy young and elderly men, but reference intervals for FT and BT were lower in elderly men due to higher levels of SHBG. Androgens and SHBG were lower in elderly men with chronic disease and inversely associated with CFM.
Abstract Introduction A diagnostic gap exists in the current dual photon X-ray absorptiometry (DXA) based diagnostic approach to osteoporosis. Other diagnostic devices have been developed, but no ...comprehensive review concerning the applicability of these diagnostic devices for population-based screening have been performed. Material and
m
ethods A systematic review of Embase, Medline and the Cochrane Central Register for Controlled Trials was performed for population-based studies that focused on technical methods that could either indicate bone mineral density (BMD) by DXA, substitute for DXA in prediction of fracture risk, or that could have an incremental value in fracture prediction in addition to DXA. Quality of included studies was rated by QUADAS 2. Results Many other technical devices have been tested in a population-based setting. Five studies aiming to indicate BMD and 17 studies aiming to predict fractures were found. Overall, the latter studies had higher methodological quality. The highest number of studies was found for quantitative ultrasound (QUS). The ability to indicate BMD or predict fractures was moderate to minor for all examined devices, using reported
a
rea
u
nder the
c
urve (AUC) of Receiver Operating Characteristic curves values as standard. Conclusions Of the methods assessed, only QUS appears capable of perhaps replacing DXA as standalone examination in the future whilst radiographic absorptiometry could provide important information in areas with scarcity of DXA. QUS may be of added value even after DXA has been performed. Evaluation of proposed cutoff-values from population-based studies in separate population-based cohorts is still lacking for most examination devices.
Summary
Osteogenesis imperfecta (OI) is a disease causing bone fragility; however, it potentially affects all organs with a high content of collagen, including ears, teeth, and eyes. The study is ...cross-sectional and compares non-skeletal characteristics in adults with OI that clinicians should be aware of when caring for patients with OI.
Introduction
Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder. The skeletal fragility is pronounced; however, OI leads to a number of extra-skeletal symptoms related to the ubiquity of collagen type 1 throughout the human body. The vast majority of knowledge is derived from studies performed in the pediatric population. Thus, we aimed to investigate the nature and prevalence of ophthalmologic, odontologic, and otologic phenotypes in an adult population with OI.
Methods
The study population comprises 85 Danish OI patients (age 44.9 ± 15.9 years). Fifty-eight patients had OI type I, 12 OI type III, and 15 OI type IV according to the classification by Sillence. Audiometric evaluations and dental examinations were performed in 62 and 73 patients, respectively. Ophthalmologic investigations were performed in 64 patients, including measurements of the central corneal thickness.
Results
All patients, except two, had corneal thickness below the normal reference value. Patients with OI type I and patients with a quantitative collagen defect had thinner corneas compared to patients with OI type III and other patients with a qualitative collagen defect. One patient in this cohort was diagnosed with and treated for acute glaucoma. Dentinogenesis imperfecta was diagnosed in one fourth of the patients, based on clinical and radiographic findings. This condition was predominately seen in patients with moderate to severe OI. Hearing loss requiring treatment was found in 15 of 62 patients, of whom three were untreated. The most prevalent type of hearing loss (HL) was sensorineural hearing loss, whereas conductive HL was solely seen in patients with OI type III. The patients with the most severe degrees of HL were patients with mild forms of OI. Age was associated with increased HL.
Conclusion
Although significant health problems outside the skeleton are frequent in adult patients with OI, the patients are not consistently monitored and treated for their symptoms. Clinicians treating adult patients with OI should be aware of non-skeletal health issues and consider including regular interdisciplinary check-ups in the management plan for adult OI patients.
Summary
Risk factors for fractures were assessed in a random sample of 4,696 elderly men followed for 5.4 years. Results highlighted the importance of assessment of falls and dizziness as well as ...novel risk factors including frequent urination and erectile dysfunction.
Introduction
Knowledge about risk factors for fracture in men is limited. The aim of this study was to evaluate factors potentially associated with fracture risk in men.
Methods
A questionnaire enquiring about potential risk factors for fractures in men was posted to a random sample of 9,314 men aged 60–74 years. A completed questionnaire was returned by 4,696 (50.4%). Follow-up on incident fractures over 5.4 years was performed using public registries.
Results
During the study, 203 individuals experienced a first clinical fracture, of which 85 patients were considered osteoporotic (9 in humerus, 10 vertebral, 32 in the hip and 34 in the forearm). Cox proportional hazard regression models were used to evaluate risk factors for
any
and
osteoporotic
fractures. The following variables were found to be associated with increased risk of
any
fracture in adjusted models family history of a hip fracture (HR; 95%CI: 1.56; 1.05–2.33), falls (2–4/year: 2.10; 1.35–3.27, >4/year: 2.46; 1.12–5.41, both compared to no falls), dizziness (2.36; 1.51–3.71), erectile dysfunction (1.41; 1.06–1.87) and frequent urination (2.06; 1.26–3.39). Similarly, falls (2.36; 1.45–3.86), dizziness (2.83; 1.52–5.25), erectile dysfunction (2.01; 1.30–3.09) and pulmonary illness (1.90; 1.03–3.53) were associated with increased risk of
osteoporotic
fractures in adjusted models.
Conclusion
These results underline the importance of assessment of dizziness, falls and those with a family history of hip fracture. Frequent urination and erectile dysfunction were independently associated with increased fracture risk. Although the mechanism of association is unknown, these variables are likely to be indicators of frailty or hypogonadism.
Summary A nationwide case-control study was performed in 62,865 men aged 50+ using fracture data from the national hospital discharge register to screen all redeemed prescriptions in the past 5 years ...for significant mapping to fracture risk, employing measures to control for false discovery rate. Introduction Osteoporosis in men is frequently related to alcohol abuse, hypogonadism, hypercalciuria, or the use of glucocorticoids. Very limited information is available on the impact of other medications on fracture risk in men. Methods We conducted a nationwide population-based case-control study collecting fracture data from the Danish National Hospital Discharge Register and prescriptions from the National Prescriptions Database (1995-2000). We included men aged 50+ years, with hospital-treated fractures in the year 2000 (n = 15,716), and age- and sex-matched controls (n = 47,149). Results We identified 3.2 million redemptions of prescriptions for 1,073 different drugs. The analysis confirmed associations between fracture risk and use of sedatives, anti-epileptics, anti-psychotics, anxiolytics, SSRI, opioids and other analgesics, loop diuretics, and glucorticoids. New associations were also found. We observed an odds ratio (OR 95% CI for any fracture) for fracture in users of dopaminergic agents (1.6 1.3-1.9) and iron compounds (1.2 1.1-1.5). The largest impact on fracture risk at population level was exerted by loop diuretics and analgesics. Conclusions An array of drugs is associated with fracture risk in men. The “prescriptiome” analysis can be used as a surveillance tool for drug-induced osteoporosis and in the planning of preventive measures.
Introduction: Studies on the association between adiponectin, body composition, and insulin resistance (IR) have been conflicting.
Aim: Our aim was to evaluate the impact of body composition on ...adiponectin and IR determined by homeostasis model assessment (HOMA) in a population-based study on relatively healthy young men, minimizing the possible effects of age, obesity, and severe comorbidity.
Design, Methods, and Subjects: A population-based, cross-sectional study of 783 men aged 20–29 yr, randomly drawn from the Danish Central Personal Registry. Adiponectin was assessed using an in-house assay, and IR was determined using HOMA. Central fat mass (CFM) and lower extremity fat mass (LEFM) was measured by dual-energy x-ray absorptiometry, and visceral adipose tissue (VAT), sc adipose tissue (SAT), and thigh fat area (TFA) were assessed by magnetic resonance imaging.
Results: Using multiple linear regression analysis, adiponectin correlated negatively with CFM (r = −0.27; P < 0.001) and SAT (r = −0.20; P < 0.001) and positively with LEFM (r = 0.19; P < 0.001) and TFA (r = 0.18; P < 0.001), whereas VAT did not associate significantly. In multiple linear regression analysis, HOMA-IR (dependent variable), correlated significantly with CFM (r = 0.27; P < 0.001) and SAT (r = 0.15; P < 0.001), whereas LEFM, VAT, or TFA did not correlate. Adiponectin was an independent predictor of HOMA-IR in both analyses (r = −0.14; P < 0.001).
Conclusion: SAT rather than VAT was inversely associated with adiponectin levels, and, interestingly, fat on the lower extremities was positively associated with adiponectin. Focusing on insulin resistance, SAT rather than VAT and TFA independently predicted a higher HOMA-IR. The observation that adiponectin was independently associated with lower HOMA-IR must be repeated in other populations.
Subcutaneous adipose tissue, rather than visceral adipose tissue, is inversely associated with adiponectin; however, fat on the lower extremities is positively associated with adiponectin.
Strontium ranelate produces an early and sustained reduction of both vertebral and nonvertebral fractures in patients ≥80 years of age.
Introduction: About 25–30% of the population burden of all ...fragility fractures in the community arise from women ≥80 years of age, because this population is at high risk for all types of fracture, particularly nonvertebral fractures. Despite this, evidence that therapies reduce the risk of both vertebral and nonvertebral fractures in this group is lacking. The aim of this study was to determine whether strontium ranelate, an agent that reduces the risk of vertebral and nonvertebral fractures in postmenopausal women >50 years of age, also reduces fractures in the elderly.
Materials and Methods: An analysis based on preplanned pooling of data from two international, phase III, randomized, placebo‐controlled, double‐blind studies (the Spinal Osteoporosis Therapeutic Intervention SOTI and TReatment Of Peripheral OSteoporosis TROPOS) included 1488 women between 80 and 100 years of age followed for 3 years. Yearly spinal X‐rays were performed in 895 patients. Only radiographically confirmed nonvertebral fractures were included.
Results: Baseline characteristics did not differ in placebo and treatment arms. In the intent‐to‐treat analysis, the risk of vertebral, nonvertebral, and clinical (symptomatic vertebral and nonvertebral) fractures was reduced within 1 year by 59% (p = 0.002), 41% (p = 0.027), and 37% (p = 0.012), respectively. At the end of 3 years, vertebral, nonvertebral, and clinical fracture risks were reduced by 32% (p = 0.013), 31% (p = 0.011), and 22% (p = 0.040), respectively. The medication was well tolerated, and the safety profile was similar to that in younger patients.
Conclusions: Treatment with strontium ranelate safely reduces the risk of vertebral and nonvertebral fractures in women with osteoporosis ≥80 years of age. Even in the oldest old, it is not too late to reduce fracture risk.
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