The incidence of fractures at various sites in newly treated patients with type 2 diabetes mellitus.

Purpose: In this descriptive study, we examined the incidence of fractures in patients with newly treated type 2 diabetes mellitus (T2D) compared to matched reference population. Methods: Participants from the UK Clinical Practice research datalink (CPRD) GOLD (1987-2017), aged ≥30 years, with a T2D diagnosis code and a first prescription for a non-insulin anti-diabetic drug (n = 124,328) were included. Cases with T2D were matched by year of birth, sex and practice to a reference population (n = 124,328), the mean follow-up was 7.7 years. Crude fracture incidence rates (IRs) and incidence rate ratios (IRRs) were calculated. Analyses were stratified by fracture site and sex and additionally adjusted for BMI, smoking status, alcohol use and history of any fracture at index date. Results: The IR of all fractures and major osteoporotic fractures was lower in T2D compared to the reference population (IRR 0.97; 95%CI 0.94-0.99). The IRs were lower for clavicle (IRR 0.67; 0.56-0.80), radius/ulna (IRR 0.81; 0.75-0.86) and vertebral fractures (0.83; 0.75-0.92) and higher for ankle (IRR 1.16; 95%CI 1.06-1.28), foot (1.11; 1.01-1.22), tibia/fibula (1.17; 1.03-1.32) and humerus fractures (1.11; 1.03-1.20). Differences in IRs at various fracture sites between T2D and the reference population were more pronounced in women than in men. In contrast, BMI adjusted IRs for all fractures (IRR 1.07; 1.04-1.10) and most individual fracture sites were significantly higher in T2D, especially in women. Conclusion: The crude incidence of all fractures was marginally lower in patients with newly treated T2D compared to the matched reference population but differed according to fracture site, especially in women. BMI adjusted analyses resulted in higher incidence rates in T2D at almost all fracture sites compared to crude incidence rates and this was more pronounced in women than in men. This implies that BMI may have a protective impact on the crude incidence of fractures, especially in women with newly treated T2D.

A head-to-head comparison of EQ-5D-5L and SF-6D in Dutch patients with fractures visiting a Fracture Liaison Service.

AIMS: This study compared the psychometric properties of EQ-5D-5L and SF-6D to assess the interchangeability of both instruments in patients with a recent fracture presenting at a Fracture Liaison Service (FLS). MATERIALS AND METHODS: Data from a prospective observational study in a Dutch FLS clinic were used. Over 3 years, subjects were interviewed at several time points using EQ-5D-5L and SF-36. Floor and ceiling effects were evaluated. Agreement was evaluated by intra-class correlation coefficients and visualized in Bland-Altman plots. Spearman's rank correlation coefficients were applied to assess convergent validity. Mann-Whitney U test or Kruskal-Wallis H test as well as effect size (ES) were used to explore known-groups validity. Responsiveness was explored using standardized response mean (SRM) and ES. For each measurement property, hypotheses on direction and magnitude of effects were formulated. RESULTS: A total of 499 patients were included. EQ-5D-5L had a considerable ceiling effect in comparison to SF-6D (21 vs. 1.2%). Moderate agreement between the (UK and Dutch) EQ-5D-5L and SF-6D was identified with intra-class correlation coefficients of 0.625 and 0.654, respectively. Bland-Altman plots revealed proportional bias as the differences in utilities between two instruments were highly dependent on the health states. High correlation between instruments was found (UK: rho = 0.758; Dutch: rho = 0.763). EQ-5D-5L and SF-6D utilities showed high correlation with physical component score but low correlation with mental component score of SF-36. Both instruments showed moderate discrimination (ES > 0.5) for subgroup by baseline fracture type, and moderate responsiveness (SRM > 0.5) in patients that sustained a subsequent fracture. CONCLUSION: Both EQ-5D-5L and SF-6D appeared to be valid utility instruments in patients with fractures attending the FLS. However, they cannot be used interchangeably given only moderate agreement was identified, and differences in utilities and ceiling effect were revealed. Comparable construct validity and responsiveness were indicated, and neither instrument was found to be clearly superior.

The EQ-5D and SF-36 as generic multi-domain questionnaires are widely used to measure the health-related quality-of-life (HRQoL) in a sample of the persons who suffer from the diseases or the general population. Their responses could be converted to patients or societal Health State Utility Values (HSUVs) with the range of 0 ("death") to 1 ("full health"). A specific application of HSUV is to calculate quality-adjusted life years as the indicator of effectiveness to evaluate whether the cost of a new intervention is justified in terms of health gains through cost-utility analysis in health economics, the evidence can be further used to inform decision-making. However, different instruments differ in construct and valuation, potentially leading to different estimates for the person's same "health state", and healthcare decisions could be compromised when researchers or decision-makers are not aware of potential differences in HSUV. Therefore, it is important to gain insight into the specific psychometric properties of these instruments, and to understand whether instruments are interchangeable. Our study is based on data from a Dutch Fracture Liaison Service (FLS is a program for secondary fracture prevention), compared the psychometric properties and interchangeability of two instruments (EQ-5D-5L and SF-6D) in patients with a recent fracture presenting at the FLS, and suggested both instruments are valid in utility elicitation in our target population. However, they cannot be used interchangeably given only moderate agreement and differences in utilities. Neither instrument was found to be clearly superior given comparable construct and longitudinal validity, but different instruments values in different aspects of HRQoL assessment.

Effectiveness and cost-effectiveness of dynamic bracing versus standard care alone in patients suffering from osteoporotic vertebral compression fractures: protocol for a multicentre, two-armed, parallel-group randomised controlled trial with 12 months of follow-up.

INTRODUCTION: Patients with osteoporosis may suffer from a fracture after minimal trauma. Osteoporotic vertebral compression fractures (OVCFs) are among the most common fractures, often leading to substantial pain. There is a need for evidence-based conservative treatment to aid in the management of OVCFs. The objective of this randomised controlled trial (RCT) is to evaluate the effectiveness and cost-effectiveness of dynamic bracing in addition to standard care for improving quality of life (QoL) in patients suffering from an OVCF. METHODS AND ANALYSIS: Ninety-eight postmenopausal women from two academic and four community hospitals with a recent symptomatic thoracolumbar OVCF will be randomised into either the standard care or dynamic bracing group. In the dynamic bracing group, the Spinova Osteo orthosis will be used in addition to standard care. Standard care comprises pain control with analgesics, physical therapy and osteoporosis medication. The primary outcome parameter is QoL 1 year after inclusion, as measured by the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41). Secondary outcome parameters are pain, pain medication used, functional disability, sagittal spinal alignment, recurrence rate of OVCFs and physical activity in daily life. A trial-based economic evaluation consisting of both cost-effectiveness analysis and cost-utility analysis will be performed based on empirical data obtained in the RCT. A process evaluation will assess the feasibility of dynamic bracing. All outcomes will be assessed at baseline, 6 weeks, 3 months, 6 months, 9 months and 12 months. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Medical Ethics Committee, University Hospital Maastricht and Maastricht University (METC azM/UM) (NL74552.068.20/METC 20-055). Patients will be included only after verification of eligibility and obtaining written informed consent. Results will be disseminated via the Dutch National Osteoporosis Patient Society and via publications and conferences. TRIAL REGISTRATION NUMBER: NL8746.

Prevalent Morphometrically Assessed Vertebral Fractures in Individuals With Type 2 Diabetes, Prediabetes and Normal Glucose Metabolism: The Maastricht Study.

BACKGROUND: Type 2 diabetes (T2D) is frequently reported to be associated with an increased fracture risk. Epidemiological data on prevalent morphometric vertebral fractures (VFs) in T2D are sparse and even less is known in the prediabetic state. PURPOSE: To determine the association between prevalence and severity of morphometric VFs and glucose metabolism state: normal glucose metabolism (NGM), impaired glucose metabolism (prediabetes) or T2D. METHODS: This study included cross-sectional data from 3625 participants of the Maastricht Study who had a vertebral fracture assessment on lateral Dual Energy X-Ray Absorptiometry images. VFs were classified based on morphometric assessment into mild, moderate and severe VFs (respectively 20-24%, 25-39% or ≥40% reduction in expected vertebral body height). Logistic regression models were used to investigate the association between glucose metabolism status and the prevalence and severity of VFs. Analyses were adjusted for subject characteristics and life-style factors. RESULTS: T2D individuals were older (62.8 ± 7.5 years old) and less often female (30.5%) compared to the NGM group (57.7 ± 8.5 years old, and 58.8% female, respectively). At least one mild, moderate or severe prevalent VF was found in 8.6% of the men and 2.2% of the women in the T2D group, in 9.4% and 8.4% in the prediabetes group and in 9.1% and 4.8% in the NGM group, respectively. After adjustment T2D in women was associated with a lower probability of having a prevalent VF compared to NGM [adjusted OR 0.25 (95% CI 0.09-0.65)], while this was not the case for prediabetes. Furthermore, women with T2D had a significantly lower probability of a prevalent moderate or severe VF [adjusted OR 0.32 (95% CI 0.11-0.96)]. In men there was no significant association between T2D or prediabetes and prevalent VFs. CONCLUSION: Women with T2D had a lower probability of prevalent VFs compared to women with a normal glucose metabolism, while this was not the case for men with T2D and participants with prediabetes.

Fracture liaison programs.

In view of the high imminent risk of having subsequent fractures after a fracture, early evaluation and treatment decisions to prevent subsequent fractures are advocated. After a hip fracture, the fracture liaison service (FLS) and orthogeriatric care are considered the most appropriate organisational approaches for secondary fracture prevention following a recent fracture. Their introduction and implementation have been shown to increase evaluation and treatment of patients at high risk for subsequent fracture. Of real-world cohort studies, most, but not all studies, indicate a lower incidence of fracture and longer survival after treatment with nitrogen-containing bisphosphonates.

Contra-lateral bone loss at the distal radius in postmenopausal women after a distal radius fracture: A two-year follow-up HRpQCT study.

Opposite to the fracture side, bone mineral density (BMD) measured by DXA at the contra-lateral side does not change after a distal radius fracture. However, it is unknown if also bone micro-architecture and strength at the contralateral side are unaffected. Therefore, the aim of this study was to assess BMD, micro-architecture and bone mechanical properties at the contra-lateral side during two years follow-up after a distal radius fracture using high resolution peripheral quantitative computed tomography (HRpQCT). The contra-lateral distal radius of 15 postmenopausal women (mean age 64±8years) with a distal radius fracture treated by cast immobilization was scanned by HRpQCT at baseline, 3months and 2years post-fracture. BMD and cortical and trabecular micro-architecture were measured and biomechanical parameters were estimated using micro finite element analysis (µFEA). Additionally, markers of bone resorption and formation were measured at each visit. Bone parameters and turnover markers across the three visits were analysed using a linear mixed-effect model with Bonferroni correction. Two years post-fracture, a significant decrease from baseline was found in cortical BMD (-4.2%, p<0.001), failure load (-6.1%, p=0.001), stiffness in compression (-5.7%, p=0.003) and bending (-6.4%, p=0.008), and bone formation (-47.6%, p=0.010). No significant changes from baseline were observed in total and trabecular BMD, nor in cortical or trabecular micro-architecture and neither in bone resorption. Results were similar between patients with or without adequate anti-osteoporosis drug treatment. We found a significant decline in BMD in the cortical but not the trabecular region, and a reduction in bone strength and stiffness at the contra-lateral side two years after a distal radius fracture. These changes exceeded the changes that may be expected due to aging, even in the presence of adequate anti-osteoporosis treatment.

A Review of Patient Preferences for Osteoporosis Drug Treatment.

Poor medication adherence is a major problem in chronic diseases such as osteoporosis that may partially be due to unaddressed patient values and preferences. Data on patient preferences could help clinicians to improve medication adherence and could also be useful in policy decisions and guideline development. This paper aims to identify literature reporting on the preferences of patients for osteoporosis drug medications. Several methods have been used to elicit patient preferences for medications and their characteristics including qualitative research, survey with ranking/rating exercises, discrete-choice experiments and clinical studies (crossover designs, open-label study). All these studies revealed that osteoporotic patients have preferences for medications and their attributes, in particular for less-frequent dosing regimens. Interestingly, variations in the preferences of patients were observed in most studies, suggesting the importance to take into account individual preference in decision-making to improve osteoporosis care.

Secondary osteoporosis and metabolic bone disease in patients 50 years and older with osteoporosis or with a recent clinical fracture: a clinical perspective.

PURPOSE OF REVIEW: The purpose of this review is to provide guidance to clinicians about which laboratory tests should be performed in patients with osteoporosis or with a recent fracture. RECENT FINDINGS: Newly diagnosed secondary osteoporosis and other metabolic bone diseases (SECOB) have been found in 5-48% of patients with osteoporosis. In patients with a recent fracture, new SECOB is found in 10-47% of patients with osteoporosis, and in 26-51% if all patients with a fracture regardless of bone mineral density (BMD) are screened. More than one SECOB can be found in the same patient, even when they have already known SECOB. In primary hyperparathyroidism, hyperthyroidism, hypercortisolism, and multiple myeloma, both SECOB and its treatment have an impact on BMD and fractures. For other SECOBs, no treatment is available, or there are no data about the effect of treatment of the SECOB on BMD and fractures. SUMMARY: We recommend performing the following tests in all patients with osteoporosis or a recent clinical fracture: calcium, phosphate, creatinine, albumin, erythrocyte sedimentation rate in all patients, 24 h urine calcium in men and serum testosterone in men less than 70 years. On indication, additional tests can be performed.

Suboptimal effect of different vitamin D3 supplementations and doses adapted to baseline serum 25(OH)D on achieved 25(OH)D levels in patients with a recent fracture: a prospective observational study.

OBJECTIVE: Guidelines on the need for dose adaptation of vitamin D3 supplementation according to baseline serum 25(OH)D are inconclusive. The effects of increasing doses of vitamin D3 at lower baseline serum 25(OH)D values on the serum 25(OH)D after 4.2 and 11 months were determined in an observational study. DESIGN: A prospective observational study. METHODS: Out of 1481 consecutive women and men with a recent clinical fracture, 707 had a baseline 25(OH)D level <50 nmol/l and were supplemented with increasing doses of vitamin D3 (400, 800, 1700, and ≥3500 IU/day) according to the lower baseline 25(OH)D. Final analysis was restricted to the 221 participants who had full follow-up data available for 11 months. RESULTS: Serum 25(OH)D ≥50 nmol/l was achieved in 57-76% of patients after 4.2 months and in 73-79% after 11 months. These percentages were similar for all doses (P=0.06 and P=0.91 respectively). The mean achieved 25(OH)D was similar for all dose groups (56.1-64.0 nmol/l after 4.2 months and 60.2-76.3 nmol/l after 11 months). With multivariate analysis, the increase in 25(OH)D (17±32.0 after 4.2 months and 24.3±34.0 nmol/l after 11 months) was dependent on the baseline 25(OH)D (P<0.001), not on supplementation dose, season, age, BMI, or gender. CONCLUSIONS: The increase in serum 25(OH)D was significantly larger with higher vitamin D3 supplementation doses. However, this dose-effect response was mainly explained by the baseline 25(OH)D, not the supplementation dose, with a greater magnitude of response at lower baseline 25(OH)D concentrations. In 21-27% of patients, serum 25(OH)D3 levels did not reach 50 nmol/l after 11 months, at any dose. Further studies are needed to identify possible causes of suboptimal response such as non-compliance, undiagnosed malabsorption syndromes, or variability in cholecalciferol content of the vitamin D supplements.

Contributors to secondary osteoporosis and metabolic bone diseases in patients presenting with a clinical fracture.

BACKGROUND: Previously undetected contributors to secondary osteoporosis and metabolic bone diseases (SECOB) are frequently found in patients with osteoporosis, but the prevalence in patients at the time they present with a clinical fracture is unknown. METHODS: All consecutive patients with a recent clinical vertebral or nonvertebral fracture, who were able and willing to be investigated (n = 626: 482 women, 144 men, age range 50-97 yr) had bone mineral density and laboratory investigations (serum calcium, inorganic phosphate, 25-hydroxyvitamin D, creatinine, intact PTH, TSH, free T(4), serum and urine protein electrophoresis, and in men also serum testosterone). RESULTS: Known SECOB contributors were present in 23.0% of patients and newly diagnosed SECOB contributors in 26.5%: monoclonal proteinemia (14 of 626), renal insufficiency grade III or greater (54 of 626), primary (17 of 626) and secondary (64 of 626) hyperparathyroidism, hyperthyroidism (39 of 626), and hypogonadism in men (12 of 144). Newly diagnosed SECOBs, serum 25-hydroxyvitamin D less than 50 nmol/liter (in 63.9%), and dietary calcium intake less than 1200 mg/d (in 90.6%) were found at any age, in both sexes, after any fracture (except SECOB in men with finger and toe fractures) and at any level of bone mineral density. CONCLUSION: At presentation with a fracture, 26.5% of patients have previously unknown contributors to SECOB, which are treatable or need follow-up, and more than 90% of patients have an inadequate vitamin D status and/or calcium intake. Systematic screening of patients with a recent fracture identifies those in whom potentially reversible contributors to SECOB and calcium and vitamin D deficiency are present.

Optimal use of vitamin D when treating osteoporosis.

Inadequate serum 25-hydroxyvitamin D (25[OH]D) concentrations are associated with muscle weakness, decreased physical performance, and increased propensity in falls and fractures. This paper discusses several aspects with regard to vitamin D status and supplementation when treating patients with osteoporosis in relation to risks and prevention of falls and fractures. Based on evidence from literature, adequate supplementation with at least 700 IU of vitamin D, preferably cholecalciferol, is required for improving physical function and prevention of falls and fractures. Additional calcium supplementation may be considered when dietary calcium intake is below 700 mg/day. For optimal bone mineral density response in patients treated with antiresorptive or anabolic therapy, adequate vitamin D and calcium supplementation is also necessary. Monitoring of 25(OH)D levels during follow-up and adjustment of vitamin D supplementation should be considered to reach and maintain adequate serum 25(OH)D levels of at least 50 nmol/L, preferably greater than 75 nmol/L in all patients.