High-resolution peripheral computed tomography (HR-pQCT) was developed to image bone microarchitecture in vivo at peripheral skeletal sites. Since the introduction of HR-pQCT in 2005, clinical ...research to gain insight into pathophysiology of skeletal fragility and to improve prediction of fractures has grown. Meanwhile, the second-generation HR-pQCT device has been introduced, allowing novel applications such as hand joint imaging, assessment of subchondral bone and cartilage thickness in the knee, and distal radius fracture healing. This article provides an overview of the current clinical applications and guidance on interpretation of results, as well as future directions. Specifically, we provide an overview of (1) the differences and reference data for HR-pQCT variables by age, sex, and race/ethnicity; (2) fracture risk prediction using HR-pQCT; (3) the ability to monitor response of anti-osteoporosis therapy with HR-pQCT; (4) the use of HR-pQCT in patients with metabolic bone disorders and diseases leading to secondary osteoporosis; and (5) novel applications of HR-pQCT imaging. Finally, we summarize the status of the application of HR-pQCT in clinical practice and discuss future directions. From the clinical perspective, there are both challenges and opportunities for more widespread use of HR-pQCT. Assessment of bone microarchitecture by HR-pQCT improves fracture prediction in mostly normal or osteopenic elderly subjects beyond DXA of the hip, but the added value is marginal. The prospects of HR-pQCT in clinical practice need further study with respect to medication effects, metabolic bone disorders, rare bone diseases, and other applications such as hand joint imaging and fracture healing. The mostly unexplored potential may be the differentiation of patients with only moderately low BMD but severe microstructural deterioration, which would have important implications for the decision on therapeutical interventions.
Given the expected increase in the number of patients with osteoporosis and fragility fractures it is important to have concise information on trends in prescription rates of anti-osteoporosis drugs ...(AOD).
We undertook a retrospective observational study using the UK Clinical Practice Research Datalink (CPRD) in the UK between 1990 and 2012 in subjects 50years or older, stratified by age, sex, geographic region and ethnicity. Yearly prescription incidence rates of any AOD and of each specific AOD were calculated as the number of patients first prescribed these AODs per 10,000person-years (py).
In women, yearly rates of first prescription of any AOD increased from 1990 to 2006 (from 2.3 to 169.7 per 10,000py), followed by a plateau and a 12% decrease in the last three years. In men, a less steep increase from 1990 to 2007 (from 1.4 to 45.3 per 10,000py) was followed by a plateau from 2008 onwards. Yearly rates of first prescription of any AOD increased up to the age of 85–89years (248.9 per 10,000py in women and 119.3 in men). There were marked differences between ethnic groups and regions. Bisphosphonates were the most frequently prescribed AODs: etidronate till 2000, and then subsequently alendronate.
We have demonstrated marked secular changes in rates of anti-osteoporosis drug prescription over the last two decades. The plateau (and decrease amongst women) in rates in recent years, set against an ever ageing population, is worrying, suggesting that the well-documented care gap in osteoporosis treatment persists. The differences in prescription rates by geographic location and ethnicity raise intriguing questions in relation to underlying fracture rates, provision of care and health behaviour.
We studied the prescription incidence of anti-osteoporosis drugs (AOD) from 1990 to 2012 in the UK CPRD. Overall AOD prescription incidence showed a strong increase from 1990 to 2006, followed by a plateau in both sexes and a decrease amongst women in the last three years.
•In UK CPRD we documented rates of anti-osteoporosis treatment by age, sex, ethnicity, geographic location and calendar time.•In women, annual rates of first prescription increased from 1990-2006 followed by a plateau and a 12% decrease 2009-2012.•In men, prescription rates increased less steeply from 1990-2007 and then levelled from 2008 onwards.•There were marked differences in anti-osteoporosis treatment rates by ethnicity and geographic location within the UK.
Alterations of structure and density of cortical bone are associated with fragility fractures and can be assessed in vivo in humans at the tibia. Bone remodeling deficits in aging women have been ...recently linked to an increase in size of cortical pores. In this ex vivo study, we characterized the cortical microarchitecture of 19 tibiae from human donors (aged 69 to 94 years) to address, whether this can reflect impairments of the mechanical competence of the proximal femur, i.e., a major fracture site in osteoporosis. Scanning acoustic microscopy (12 μm pixel size) provided reference microstructural measurements at the left tibia, while the bone vBMD at this site was obtained using microcomputed tomography (microCT). The areal bone mineral density of both left and right femoral necks (aBMDneck) was measured by dual-energy X-ray absorptiometry (DXA), while homogenized nonlinear finite element models based on high-resolution peripheral quantitative computed tomography provided hip stiffness and strength for one-legged standing and sideways falling loads. Hip strength was associated with aBMDneck (r = 0.74 to 0.78), with tibial cortical thickness (r = 0.81) and with measurements of the tibial cross-sectional geometry (r = 0.48 to 0.73) of the same leg. Tibial vBMD was associated with hip strength only for standing loads (r = 0.59 to 0.65). Cortical porosity (Ct.Po) of the tibia was not associated with any of the femoral parameters. However, the proportion of Ct.Po attributable to large pores (diameter > 100 μm) was associated with hip strength in both standing (r = -0.61) and falling (r = 0.48) conditions. When added to aBMDneck, the prevalence of large pores could explain up to 17% of the femur ultimate force. In conclusion, microstructural characteristics of the tibia reflect hip strength as well as femoral DXA, but it remains to be tested whether such properties can be measured in vivo.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
In this small cross-sectional study of predominantly well-treated participants with relatively short-term type 2 diabetes duration, HbA1c > 7% (53 mmol/mol) was associated with lower cortical ...density and thickness and higher cortical porosity at the distal radius, lower trabecular thickness at the distal tibia, and higher trabecular number at both sites.
Introduction
To examine the association between diabetes status and volumetric bone mineral density (vBMD), bone microarchitecture and strength of the distal radius and tibia as assessed with HR-pQCT. Additionally—in participants with type 2 diabetes (T2DM), to examine the association between HbA1c, diabetes duration, and microvascular disease (MVD) and bone parameters.
Methods
Cross-sectional data from 410 (radius) and 198 (tibia) participants of The Maastricht Study (mean age 58 year, 51% female). Diabetes status (normal glucose metabolism, prediabetes, or T2DM) was based on an oral glucose tolerance test and medication history.
Results
After full adjustment, prediabetes and T2DM were not associated with vBMD, bone microarchitecture, and strength of the radius and tibia, except for lower trabecular number (Tb.N) of the tibia (− 4%) in prediabetes and smaller cross-sectional area of the tibia (− 7%) in T2DM. In T2DM, HbA1c > 7% was associated with lower cortical vBMD (− 5%), cortical thickness (− 16%), higher cortical porosity (+ 20%) and Tb.N (+ 9%) of the radius, and higher Tb.N (+ 9%) and lower trabecular thickness (− 13%) of the tibia. Diabetes duration > 5 years was associated with higher Tb.N (+ 6%) of the radius. The presence of MVD was not associated with any bone parameters.
Conclusions
In this study with predominantly well-treated T2DM participants with relatively short-term diabetes duration, inadequate blood glucose control was negatively associated with cortical bone measures of the radius. In contrast, trabecular number was increased at both sites. Studies of larger sample size are warranted for more detailed investigations of bone density and bone quality in patients with T2DM.
Summary
We studied sex-specific incidence rates in a population 50 years or older in the UK. In the period of 1990–2012, the overall rate of fracture did not change, but there were marked secular ...alterations in the rates of individual fracture types, particularly hip and spine fractures in the elderly.
Introduction
There is increasing evidence of secular changes in age- and sex- adjusted fracture incidence globally. Such observations broadly suggest decreasing rates in developed countries and increasing rates in transitioning populations. Since altered fracture rates have major implications for healthcare provision and planning, we investigated secular changes to age- and sex-adjusted fracture risk amongst the UK population aged 50 years or above from 1990 till 2012.
Methods
We undertook a retrospective observational study using the Clinical Practice Research Datalink (CPRD), which contains the health records of 6.9 % of the UK population. Site-specific fracture incidence was calculated by calendar year for men and women separately, with fracture type categorised according to ICD-9 classification. Linear regression analysis was used to calculate mean annualised change in absolute incidence. For presentational purposes, mean rates in the first 5 years and last 5 years of the period were calculated.
Results
Overall fracture incidence was unchanged in both women and men from 1990 to 2012. The incidence of hip fracture remained stable amongst women (1990–1994 33.8 per 10,000 py; 2008–2012 33.5 per 10,000 py;
p
trend annualised change in incidence = 0.80) but rose in men across the same period (10.8 to 13.4 per 10,000 py;
p
= 0.002). Clinical vertebral fractures became more common in women (8.9 to 11.8 per 10,000 py;
p
= 0.005) but remained comparable in men (4.6 to 5.9 per 10,000 py;
p
= 0.72). Similarly, the frequency of radius/ulna fractures did not change in men (9.6 to 9.6 per 10,000 py;
p
= 0.25), but, in contrast, became less frequent in women (50.4 to 41.2 per 10,000 py;
p
= 0.001). Secular trends amongst fractures of the carpus, scapula, humerus, foot, pelvis, skull, clavicle, ankle, patella, and ribs varied according to fracture site and sex.
Conclusion
Although overall sex-specific fracture incidence in the UK population 50 years or over appears to have remained stable over the last two decades, there have been noticeable changes in rates of individual fracture types. Given that the impact of a fracture on morbidity, mortality, and health economy varies according to fracture site, these data inform the provision of healthcare services in the UK and elsewhere.
Background
Long‐term use of antiseizure drugs is associated with a low bone mineral density (BMD) and an increased fracture risk. The literature regarding institutionalised children on chronic ...antiseizure drugs is limited. Therefore, the aim of this cross‐sectional study is to evaluate the prevalence of low BMD and the history of fractures in institutionalised children with epilepsy and intellectual disability (ID).
Methods
A dual‐energy X‐ray absorptiometry of lumbar spine (L1–L4) and hip was performed in 24 children, residing in a long‐stay care facility in the Netherlands. Additionally, serum concentrations of albumin, calcium and 25‐hydroxyvitamin D were determined. Data on fractures were retrospectively extracted from the medical files.
Results
Ages of the children (14 male and 10 female) ranged from 5 to 17 years with a mean age of 13.0 (±3.2). The criteria of the International Society for Clinical Densitometry (ISCD) were used for classification of bone mineral disorders. Eight (33.3%) children had a normal BMD (Z‐score > − 2.0). Of the 16 children with a low BMD (Z‐score ≤ − 2.0), three were diagnosed as osteoporotic, based on their fracture history. Ten children (41.7%) were reported to have at least one fracture in their medical history. Serum concentrations of albumin‐corrected calcium (2.28–2.50 mmol/L) and (supplemented) vitamin D (16–137 nmol/L) were within the normal range.
Conclusions
This study demonstrated that 67% of institutionalised children with epilepsy and ID had low BMD and 42% had a history of at least one fracture, despite supplementation of calcium and vitamin D in accordance with the Dutch guidelines.
Summary
This systematic review and meta-analysis suggests that fracture liaison service (FLS) is associated with a significantly lower probability of subsequent fractures and mortality although the ...latter was only found in studies comparing outcomes before and after the introduction of an FLS.
Introduction
To systematically review and evaluate the impact of fracture liaison services (FLSs) on subsequent fractures and mortality using meta-analysis.
Methods
A literature search was performed within PubMed and Embase to identify original articles published between January 1, 2010, and April 30, 2020, reporting the effect of FLSs on subsequent fractures and/or mortality. Only studies comparing FLS to no-FLS were included. A meta-analysis using random-effects models was conducted. The quality of studies was appraised after combining and modifying criteria of existing quality assessment tools.
Results
The search retrieved 955 published studies, of which 16 studies fulfilled the inclusion criteria. Twelve studies compared outcomes before (pre-FLS) and after (post-FLS) FLS implementation, two studies compared outcomes between hospitals with and without FLS, and two other studies performed both comparisons. In total, 18 comparisons of FLS and no-FLS care were reported. Follow-up time varied from 6 months to 4 years. Sixteen comparisons reported on subsequent fractures and 12 on mortality. The quality assessment revealed methodological issues in several criteria. Excluding studies with very high selection bias, the meta-analysis of nine comparisons (in eight papers) revealed that the FLS care was associated with a significantly lower probability of subsequent fractures (odds ratio: 0.70, 95% CI: 0.52–0.93,
P
=0.01). In studies with a follow-up > 2 years, a significantly lower probability of subsequent fractures was captured for FLS care (odds ratio: 0.57, 95% CI: 0.34–0.94,
P
=0.03), while in studies ≤ 2 years, there was no difference in the odds of subsequent fractures. No significant difference in the odds of mortality was observed (odds ratio: 0.73, 95% CI: 0.49–1.09,
P
=0.12) in the meta-analysis of eight comparisons (in seven papers). However, a significantly lower probability of mortality was identified in the six pre-post FLS comparisons (odds ratio: 0.65, 95% CI: 0.44–0.95,
P
=0.03), but not in studies comparing hospitals with and without FLS. No difference was observed in mortality stratified by follow-up time.
Conclusion
This systematic review and meta-analysis suggests that FLS care is associated with a significantly lower probability of subsequent fractures and mortality although the latter was only found in studies comparing outcomes before and after the introduction of an FLS. The quality assessment revealed that some important methodological issues were unmet in the currently available studies. Recommendations to guide researchers to design high-quality studies for evaluation of FLS outcomes in the future were provided.
Summary
In this retrospective cohort study using the Clinical Practice Research Datalink (CPRD), patients with sarcoidosis have an increased risk of clinical vertebral fractures and when on recent ...treatment with oral glucocorticoids, also an increased risk of any fractures and osteoporotic fractures.
Introduction
Sarcoidosis is a chronic inflammatory disease, in which fragility fractures have been reported despite normal BMD. The aim of this study was to assess whether patients with sarcoidosis have an increased risk of clinical fractures compared to the general population.
Methods
A retrospective cohort study was conducted using the CPRD. All patients with a CPRD code for sarcoidosis between January 1987 and September 2012 were included. Cox proportional hazards models were used to derive adjusted relative risks (RRs) of fractures in all sarcoidosis patients compared to matched controls, and within the sarcoidosis group according to use and dose of systemic glucocorticoids.
Results
Five thousand seven hundred twenty-two sarcoidosis patients (mean age 48.0 years, 51 % females, mean follow-up 6.7 years) were identified.
Compared to 28,704 matched controls, the risk of any fracture was not different in patients with sarcoidosis. However, the risk of clinical vertebral fractures was significantly increased (adj RR 1.77; 95 % CI 1.06–2.96) and the risk of non-vertebral fractures was decreased although marginally significant (adj RR 0.87; 95 % CI 0.77–0.99). Compared to sarcoidosis patients not taking glucocorticoids, recent use of systemic glucocorticoids was associated with an increased risk of any fracture (adj RR 1.50; 95 % CI 1.20–1.89) and of an osteoporotic fracture (adj RR 1.47; 95 % CI 1.07–2.02).
Conclusions
Patients with sarcoidosis have an increased risk of clinical vertebral fractures, and when using glucocorticoid therapy, an increased risk of any fractures and osteoporotic fractures. In contrast, the risk of non-vertebral fractures maybe decreased. Further investigation is needed to understand the underlying mechanisms of these contrasting effects on fracture risk.
Summary
Vertebral fracture (VF) locations are bimodally distributed in the spine. The association between VF and bone attenuation (BA) measured on chest CT scans varied according to the location of ...VFs, indicating that other factors than only BA play a role in the bimodal distribution of VFs.
Introduction
Vertebral fractures (VFs) are associated with low bone mineral density but are not equally distributed throughout the spine and occur most commonly at T7–T8 and T11–T12 (“cVFs”) and less commonly at T4–T6 and T9–T10 (“lcVF”). We aimed to determine whether associations between bone attenuation (BA) and VFs vary between subjects with cVFs only, with lcVFs only and with both cVFs and lcVFs.
Methods
Chest CT images of T4–T12 in 1237 smokers with and without COPD were analysed for prevalent VFs according to the method described by Genant (11,133 vertebrae). BA (expressed in Hounsfield units) was measured in all non-fractured vertebrae (available for 10,489 vertebrae). Linear regression was used to compare mean BA, and logistic regression was used to estimate the association of BA with prevalent VFs (adjusted for age and sex).
Results
On vertebral level, the proportion of cVFs was significantly higher than of lcVF (5.6% vs 2.0%). Compared to subjects without VFs, BA was 15% lower in subjects with cVFs (
p
< 0.0001), 25% lower in subjects with lcVFs (
p
< 0.0001) and lowest in subjects with cVFs and lcVFs (− 32%,
p
< 0.0001). The highest ORs for presence of VFs per − 1SD BA per vertebra were found in subjects with both cVFs and lcVFs (3.8 to 4.6).
Conclusions
The association between VFs and BA differed according to VF location. ORs increased from subjects with cVFs to subjects with lcVFs and were highest in subjects with cVFs and lcVFs, indicating that other factors than only BA play a role in the bimodal VF distribution.
Trial registration
Clinicaltrials.gov
identifier: NCT00292552
Summary
Patients with diabetes have an increased risk of fractures. In this study, subtrochanteric and femoral shaft fractures were increased in patients with type 1 diabetes compared with the ...general population. In the light of this, more evidence points towards an association between diabetes and atypical femoral fractures.
Introduction
Patients with diabetes have an increased risk of femoral fractures, but little is known about the risk of atypical femoral fractures (AFFs). The aim of this study was to identify the risk of subtrochanteric and femoral shaft (ST/FS) fractures and estimate the risk of AFFs in patients with type 1 (T1D) and type 2 diabetes (T2D).
Methods
From the nationwide Danish National Patient Register, we identified patients with T1D (
n
= 19,896), T2D (
n
= 312,188), and sex- and aged-matched controls without diabetes (
n
= 996,252) from the general population and all ST/FS fractures (
n
= 7509). Data were analyzed using a Cox proportional-hazards model and the incidence rate and rate ratio of ST/FS fractures were estimated.
Results
The incidence rate of ST/FS fractures in T1D was 52.14 events per 100,000 person years and 73.21 per 100,000 person years in T2D. T1D was associated with an increased risk of ST/FS (HR 2.07 (95% CI 1.68–2.56)), whereas T2D was not (HR 0.99 (95% CI 0.94–1.10)). Previous ST/FS fractures were associated with an increased risk of subsequent ST/FS fractures (HR 6.95 (95% CI 6.00–8.05)) and the use of bisphosphonates with an increased risk of ST/FS fractures (HR 1.72 (95% CI 1.54–1.91)).
Conclusion
Patients with T1D have a higher risk of ST/FS fractures compared with sex- and age-matched controls. Since a proportion of ST/FS fractures are classified as AFFs, this could point towards the fact that AFFs also are increased in patients with T1D, but not T2D.
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