Mortality risk reduction differs according to bisphosphonate class: a 15-year observational study.

In this prospective cohort of 6120 participants aged 50+, nitrogen-bisphosphonates but not non-nitrogen bisphosphonates were associated with a significant 34% mortality risk reduction compared to non-treated propensity score matched controls. These findings open new avenues for research into mechanistic pathways. INTRODUCTION: Emerging evidence suggests that bisphosphonates (BP), first-line treatment of osteoporosis, are associated with reduced risks for all-cause mortality. This study aimed to determine the association between different BP types and mortality risk in participants with or without a fracture. METHODS: A prospective cohort study of users of different BPs matched to non-users by propensity score (age, gender, co-morbidities, fragility fracture status) and time to starting the BP medication from the population-based Canadian Multicentre Osteoporosis Study from nine Canadian centres followed from 1995 to 2013. Mortality risk for bisphosphonate users vs matched non-users was assessed using pairwise multivariable Cox proportional hazards models. RESULTS: There were 2048 women and 308 men on BP and 1970 women and 1794 men who did not receive medication for osteoporosis. The relationship between BP and mortality risk was explored in three separate 1:1 propensity score-matched cohorts of BP users and no treatment (etidronate, n = 599, alendronate, n = 498, and risedronate n = 213). Nitrogen BP (n-BP) (alendronate and risedronate) was associated with lower mortality risks [pairwise HR, 0.66 (95% CI, 0.48-0.91)] while the less potent non-n-BP, etidronate, was not [pairwise HR: 0.89 (95% CI, 0.66-1.20)]. A direct comparison between n-BP and etidronate (n = 340 pairs) also suggested a better survival for n-BP [paired HR, 0.47 (95%CI, (95% CI, 031-0.70)] for n-BP vs. etidronate]. CONCLUSION: Compared to no treatment, nitrogen but not non-nitrogen bisphosphonates appear to be associated with better survival.

The association between diabetes status, HbA1c, diabetes duration, microvascular disease, and bone quality of the distal radius and tibia as measured with high-resolution peripheral quantitative computed tomography-The Maastricht Study.

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.

EULAR/EFORT recommendations for management of patients older than 50†years with a fragility fracture and prevention of subsequent fractures.

The European League Against Rheumatism (EULAR) and the European Federation of National Associations of Orthopaedics and Traumatology (EFORT) have recognised the importance of optimal acute care for the patients aged 50 years and over with a recent fragility fracture and the prevention of subsequent fractures in high-risk patients, which can be facilitated by close collaboration between orthopaedic surgeons and rheumatologists or other metabolic bone experts. Therefore, the aim was to establish for the first time collaborative recommendations for these patients. According to the EULAR standard operating procedures for the elaboration and implementation of evidence-based recommendations, 7 rheumatologists, a geriatrician and 10 orthopaedic surgeons met twice under the leadership of 2 convenors, a senior advisor, a clinical epidemiologist and 3 research fellows. After defining the content and procedures of the task force, 10 research questions were formulated, a comprehensive and systematic literature search was performed and the results were presented to the entire committee. 10 recommendations were formulated based on evidence from the literature and after discussion and consensus building in the group. The recommendations included appropriate medical and surgical perioperative care, which requires, especially in the elderly, a multidisciplinary approach including orthogeriatric care. A coordinator should setup a process for the systematic investigations for future fracture risk in all elderly patients with a recent fracture. High-risk patients should have appropriate non-pharmacological and pharmacological treatment to decrease the risk of subsequent fracture.

The association between glucose metabolism status, diabetes severity and a history of fractures and recent falls in participants of 50 years and older-the Maastricht Study.

In this cohort of relatively young and well-treated participants with type 2 diabetes, we found no association between diabetes status and a history of previous fractures and recent falls. Furthermore, no association between diabetes severity and previous fractures or recent falls was found. INTRODUCTION: In this study, we examined the association between glucose metabolism status and historical fractures or recent falls and the effect of diabetes severity (glucose control, insulin use, and diabetes duration) on falls and fractures in the participants with type 2 diabetes. METHODS: Cross-sectional data from 2005 participants of the Maastricht Study. Falls in the past 6 months and fractures ≥age 50 were assessed by questionnaire. Glucose metabolism status (normal glucose metabolism, impaired glucose metabolism, or type 2 diabetes) was based on the oral glucose tolerance test and medication use. RESULTS: In the completely adjusted model, the odds for a fall were not significantly higher in those with impaired glucose metabolism status (OR (95%CI) 1.28 (0.93-1.77)) or with type 2 diabetes (OR (95%CI) 1.21 (0.80-1.81)) compared with the group with normal glucose metabolism. Within the group with type 2 diabetes, there were no significant differences with regard to reported falls between participants with HbA1c >7 % (53 mmol/mol) versus HbA1c ≤7 % (OR (95%CI) 1.05 (0.58-1.90)), insulin users versus non-insulin users (OR (95%CI) 1.51 (0.79-2.89)), and with a diabetes duration >5 versus ≤5 years (OR (95%CI) 0.52 (0.46-1.47)). Similarly, neither glucose metabolism status nor diabetes severity was associated with prior fractures. CONCLUSIONS: Glucose metabolism status was not significantly associated with previous fractures and recent falls. In addition, in this cohort of relatively young and well-treated participants with type 2 diabetes, diabetes severity was not associated with previous fractures and recent falls.

Implementation of osteoporosis guidelines: a survey of five large fracture liaison services in the Netherlands.

SUMMARY: Implementation of case findings according to guidelines for osteoporosis in fracture patients presenting at a Fracture Liaison Service (FLS) was evaluated. Despite one guideline, all FLSs differed in the performance of patient selection and prevalence of clinical risk factors (CRFs) indicating the need for more concrete and standardised guidelines. INTRODUCTION: The aim of the study was to evaluate the implementation of case findings according to guidelines for osteoporosis in fracture patients presenting at FLSs in the Netherlands. METHODS: Five FLSs were contacted to participate in this prospective study. Patients older than 50 years with a recent clinical fracture who were able and were willing to participate in fracture risk evaluation were included. Performance was evaluated by criteria for patient recruitment, patient characteristics, nurse time, evaluated clinical risk factors (CRFs), bone mineral density (BMD) and laboratory testing and results of CRFs and BMD are presented. Differences between FLSs were analysed for performance (by chi-square and Student's t test) and for prevalence of CRFs (by relative risks (RR)). RESULTS: All FLSs had a dedicated nurse spending 0.9 to 1.7 h per patient. During 39 to 58 months follow-up, 7,199 patients were evaluated (15 to 47 patients/centre/month; mean age, 67 years; 77% women). Major differences were found between FLSs in the performance of patient recruitment, evaluation of CRFs, BMD and laboratory testing, varying between 0% and 100%. The prevalence of CRFs and osteoporosis varied significantly between FLSs (RR between 1.7 and 37.0, depending on the risk factor). CONCLUSION: All five participating FLSs with a dedicated fracture nurse differed in the performance of patient selection, CRFs and in the prevalence of CRFs, indicating the need for more concrete and standardised guidelines to organise evaluation of patients at the time of fracture in daily practice.

Risk of subsequent fracture and mortality within 5 years after a non-vertebral fracture.

SUMMARY: The absolute 5-year risk of subsequent non-vertebral fractures (NVFs) in 1,921 patients presenting with a NVF was 17.6% and of mortality was 32.3%. These risks were highest within the first year, indicating the need to study which reversible factors can be targeted to immediately minimise subsequent fracture risk and mortality. INTRODUCTION: NVFs are the most frequent clinical fractures in patients presenting at the emergency unit because of a clinical fracture. The aim of the study was to determine the 5-year absolute risk (AR) of subsequent NVF and mortality in patients at the time they present with a NVF. METHODS: Between 1999 and 2001, 1,921 consecutive patients 50+ years from a level 1 trauma centre were included. All NVFs were confirmed on radiograph reports, and mortality was checked in the national obituary database. Available potential risk factors for a subsequent NVF and mortality (age, sex and baseline fracture location: major-hip, pelvis, multiple ribs, proximal tibia/humerus and distal femur; minor-all others) were expressed as hazard ratios (HR) with 95% confidence intervals (CI) using multivariable Cox regression analysis. RESULTS: The AR for a subsequent NVF was 17.6% and was related to age (HR per decade, 1.44; 95%CI, 1.29-1.60). The AR for mortality was 32.3% and was related to age (HR per decade, 2.59; 95%CI, 2.37-2.84), male sex (HR, 1.74; 95%CI, 1.44-2.10), major fracture at baseline (HR, 5.56; 95%CI, 3.48-8.88; not constant over time) and subsequent fracture (HR, 1.65; 95%CI, 1.33-2.05). The highest risks were found within the first year (NVFs, 6.4%; mortality, 12.2%) and were related to age and, in addition, to baseline fracture location for mortality. CONCLUSIONS: Within 5 years after an initial NVF, nearly one in five patients sustained a subsequent NVF and one in three died. One third of subsequent NVFs and mortality occurred within 1 year, indicating the need to study which reversible factors can be targeted to immediately prevent subsequent fractures and mortality.

Clinical subsequent fractures cluster in time after first fractures.

OBJECTIVES: The risk of subsequent fractures is double the risk of having a first fracture. We analysed whether this risk is constant or not over time. METHODS: A population-based study in 4140 postmenopausal women, aged between 50 and 90 years, on radiographic confirmed clinical fractures from menopause onwards analysed by Cox regression. RESULTS: A total of 924 (22%) women had a first fracture and 243 (26% of 924) a subsequent fracture. Of all first fractures, 4% occurred in each year from menopause onwards, while after a first fracture 23% of all subsequent fractures occurred within 1 year and 54% within 5 years. When calculated from time of first fracture, the relative risk (RR) of subsequent fracture was 2.1 (95% CI 1.7 to 2.6) and remained increased over 15 years. When calculated for specific time intervals after a first fracture, the RR was 5.3 (95% CI 4.0 to 6.6) within 1 year, 2.8 (95% CI 2.0 to 3.6) within 2-5 years, 1.4 (95% CI 1.0 to 1.8) within 6-10 years and 0.41 (95% CI 0.29 to 0.53) after >10 years. CONCLUSIONS: From menopause onwards, clinical fractures cluster in time, indicating the need for early action to prevent subsequent fractures.

The risks of sarcopenia, falls and fractures in patients with type 2 diabetes mellitus.

Fracture risk in patients with type 2 diabetes mellitus (T2DM) is increased, and the mechanism is multifactorial. Recent research on T2DM-induced bone fragility shows that bone mineral density (BMD) is often normal or even slightly elevated. However, bone turnover may be decreased and bone material and microstructural properties are altered, especially when microvascular complications are present. Besides bone fragility, extra-skeletal factors leading to an increased propensity to experience falls may also contribute to the increased fracture risk in T2DM, such as peripheral neuropathy, retinopathy and diabetes medication (e.g. insulin use). One of the probable additional contributing factors to the increased fall and fracture risks in T2DM is sarcopenia, the age-related decline in skeletal muscle mass, quality and function. Although the association between sarcopenia, fall risk, and fracture risk has been studied in the general population, few studies have examined the association between T2DM and muscle tissue and the risks of falls and fractures. This narrative review provides an overview of the literature regarding the multifactorial mechanisms leading to increased fracture risk in patients with T2DM, with a focus on sarcopenia and falls.

The association between insulin use and volumetric bone mineral density, bone micro-architecture and bone strength of the distal radius in patients with type 2 diabetes - The Maastricht study.

Type 2 diabetes mellitus (T2DM) has been associated with an increased risk of fractures, despite normal to increased bone mineral density (BMD). Insulin use is one of the factors linked to this increased fracture risk. However, direct negative effects of insulin on bone quality are not expected since insulin is thought to be anabolic to bone. In this cross-sectional study the association between insulin use and volumetric BMD (vBMD), bone micro-architecture and bone strength of the distal radius, as measured with HR-pQCT, was examined. Data from 50 participants with T2DM of The Maastricht Study (mean age 62±7.5years, 44% women) was used. Participants were classified as insulin user (n=13) or non-insulin user (n=37) based on prescription data. Linear regression analysis was used to estimate the association between current insulin use and HR-pQCT derived parameters. After adjustment for age, sex, body mass index, glycated hemoglobin A1c and T2DM duration, insulin use was associated with lower total vBMD (standardized beta (ß):-0.56 (95% CI:-0.89 to -0.24)), trabecular vBMD (ß:-0.58 (95% CI:-0.87 to -0.30)), trabecular thickness (ß:-0.55 (95% CI:-0.87 to -0.23)), cortical thickness (ß:-0.41 (95% CI:-0.74 to -0.08)), log cortical pore volume (ß:-0.43 (95% CI:-0.73 to -0.13)), bone stiffness (ß:-0.39 (95% CI:-0.62 to -0.17)) and failure load (ß:-0.39 (95% CI:-0.60 to -0.17)) when compared to the non-insulin users. Insulin use was not associated with cortical vBMD, trabecular number, trabecular separation, cortical porosity and cortical pore diameter. This study indicates that insulin use is negatively associated with bone density, bone micro-architectural and bone strength parameters. These findings may partly explain the previously observed increased fracture risk in insulin users, although there may be residual confounding by other factors related to disease severity in insulin users.