Quality of life after hip, vertebral, and distal forearm fragility fractures measured using the EQ-5D-3L, EQ-VAS, and time-trade-off: results from the ICUROS.

INTRODUCTION: The International Costs and Utilities Related to Osteoporotic fractures Study is a multinational observational study set up to describe the costs and quality of life (QoL) consequences of fragility fracture. This paper aims to estimate and compare QoL after hip, vertebral, and distal forearm fracture using time-trade-off (TTO), the EuroQol (EQ) Visual Analogue Scale (EQ-VAS), and the EQ-5D-3L valued using the hypothetical UK value set. METHODS: Data were collected at four time-points for five QoL point estimates: within 2 weeks after fracture (including pre-fracture recall), and at 4, 12, and 18 months after fracture. Health state utility values (HSUVs) were derived for each fracture type and time-point using the three approaches (TTO, EQ-VAS, EQ-5D-3L). HSUV were used to estimate accumulated QoL loss and QoL multipliers. RESULTS: In total, 1410 patients (505 with hip, 316 with vertebral, and 589 with distal forearm fracture) were eligible for analysis. Across all time-points for the three fracture types, TTO provided the highest HSUVs, whereas EQ-5D-3L consistently provided the lowest HSUVs directly after fracture. Except for 13-18 months after distal forearm fracture, EQ-5D-3L generated lower QoL multipliers than the other two methods, whereas no equally clear pattern was observed between EQ-VAS and TTO. On average, the most marked differences between the three approaches were observed immediately after the fracture. CONCLUSIONS: The approach to derive QoL markedly influences the estimated QoL impact of fracture. Therefore the choice of approach may be important for the outcome and interpretation of cost-effectiveness analysis of fracture prevention.

Geometry-Dependent Elastic Flow Dynamics in Micropillar Arrays.

Regular device-scale DNA waves for high DNA concentrations and flow velocities have been shown to emerge in quadratic micropillar arrays with potentially strong relevance for a wide range of microfluidic applications. Hexagonal arrays constitute another geometry that is especially relevant for the microfluidic pulsed-field separation of DNA. Here, we report on the differences at the micro and macroscopic scales between the resulting wave patterns for these two regular array geometries and one disordered array geometry. In contrast to the large-scale regular waves visible in the quadratic array, in the hexagonal arrays, waves occur in a device-scale disordered zig-zag pattern with fluctuations on a much smaller scale. We connect the large-scale pattern to the microscopic flow and observe flow synchronization that switches between two directions for both the quadratic and hexagonal arrays. We show the importance of order using the disordered array, where steady-state stationary and highly fluctuating flow states persist in seemingly random locations across the array. We compare the flow dynamics of the arrays to that in a device with sparsely distributed pillars. Here, we observe similar vortex shedding, which is clearly observable in the quadratic and disordered arrays. However, the shedding of these vortices couples only in the flow direction and not laterally as in the dense, ordered arrays. We believe that our findings will contribute to the understanding of elastic flow dynamics in pillar arrays, helping us elucidate the fundamental principles of non-Newtonian fluid flow in complex environments as well as supporting applications in engineering involving e.g., transport, sorting, and mixing of complex fluids.

Metabolic Syndrome Traits Increase the Risk of Major Adverse Liver Outcomes in Type 2 Diabetes.

OBJECTIVE: Type 2 diabetes (T2D) increases the risk for major adverse liver outcomes (MALOs), including cirrhosis and its complications. Patients with T2D frequently have other traits of the metabolic syndrome (MetS). It remains uncertain whether there is a synergistic effect of accumulating MetS traits on future MALO risk. RESEARCH DESIGN AND METHODS: Patients with T2D without a history of liver disease were identified from national registers in Sweden from 1998 to 2021. MetS traits included hypertension, low HDL level, hypertriglyceridemia, obesity, and albuminuria, in addition to T2D. MALO events were identified based on administrative coding from national registers until 31 October 2022. Data were analyzed using Cox regression models. RESULTS: In total, 230,992 patients were identified (median age 64 years; 58% male), of whom 3,215 (1.39%) developed MALOs over a median follow-up of 9.9 years. Compared with patients with one MetS trait (only T2D) at baseline, those with more than one MetS trait had a higher rate of MALOs (adjusted hazard ratio [aHR] 2.33, 95% CI 1.53-3.54). The rate of MALOs increased progressively with increasing numbers of MetS traits at baseline (aHR 1.28 per added trait, 95% CI 1.23-1.33). During follow-up, patients who acquired additional MetS traits had a progressively higher rate of MALOs. The MetS trait with the largest association with incident MALOs was hypertension (aHR 2.06, 95% CI 1.57-2.71). CONCLUSIONS: Having or acquiring additional traits of MetS increase the rate of progression to MALOs in patients with T2D. These results could be used to inform screening initiatives for liver disease.

Photophysical image analysis: Unsupervised probabilistic thresholding for images from electron-multiplying charge-coupled devices.

We introduce the concept photophysical image analysis (PIA) and an associated pipeline for unsupervised probabilistic image thresholding for images recorded by electron-multiplying charge-coupled device (EMCCD) cameras. We base our approach on a closed-form analytic expression for the characteristic function (Fourier-transform of the probability mass function) for the image counts recorded in an EMCCD camera, which takes into account both stochasticity in the arrival of photons at the imaging camera and subsequent noise induced by the detection system of the camera. The only assumption in our method is that the background photon arrival to the imaging system is described by a stationary Poisson process (we make no assumption about the photon statistics for the signal). We estimate the background photon statistics parameter, λbg, from an image which contains both background and signal pixels by use of a novel truncated fit procedure with an automatically determined image count threshold. Prior to this, the camera noise model parameters are estimated using a calibration step. Utilizing the estimates for the camera parameters and λbg, we then introduce a probabilistic thresholding method, where, for the first time, the fraction of misclassified pixels can be determined a priori for a general image in an unsupervised way. We use synthetic images to validate our a priori estimates and to benchmark against the Otsu method, which is a popular unsupervised non-probabilistic image thresholding method (no a priori estimates for the error rates are provided). For completeness, we lastly present a simple heuristic general-purpose segmentation method based on the thresholding results, which we apply to segmentation of synthetic images and experimental images of fluorescent beads and lung cell nuclei. Our publicly available software opens up for fully automated, unsupervised, probabilistic photophysical image analysis.

Short and long-range cyclic patterns in flows of DNA solutions in microfluidic obstacle arrays.

We observe regular patterns emerging across multiple length scales with high-concentration DNA solutions in microfluidic pillar arrays at low Reynolds numbers and high Deborah numbers. Interacting vortices between pillars lead to long-range order in the form of large travelling waves consisting of DNA at high concentration and extension. Waves are formed in quadratic arrays of pillars, while randomizing the position of the pillar in each unit cell of a quadratic array leads to suppression of the long-range patterns. We find that concentrations exceeding the overlap concentration of the DNA enables the waves, and exploring the behavior of the waves as a function of flow rate, buffer composition, concentration and molecular length, we identify elastic effects as central to the origin of the waves. Our work may not only help increase the low throughput that often limits sample processing in microfluidics, it may also provide a platform for further studies of the underlying viscoelastic mechanisms.

Using symmetry to control viscoelastic waves in pillar arrays.

Solutions of macromolecules exhibit viscoelastic properties and unlike Newtonian fluids, they may break time-reversal symmetry at low Reynolds numbers resulting in elastic turbulence. Furthermore, under some conditions, instead of the chaotic turbulence, the result is large-scale waves in the form of cyclic spatial and temporal concentration variations, as has been shown for macromolecular DNA flowing in microfluidic pillar arrays. We here demonstrate how altering the symmetry of the individual pillars can be used to influence the symmetry of these waves. We control the extent of instabilities in viscoelastic flow by leveraging the effects of the symmetry of the pillars on the waves, demonstrating suppressed viscoelastic fluctuations with relevance for transport and sorting applications, or conversely opening up for enhanced viscoelasticity-mediated mixing. The onset of waves, which changes flow resistance, occurs at different Deborah numbers for flow in different directions through the array of triangular pillars, thus breaking the symmetry of the flow resistance along the device, opening up for using the occurrence of the waves to construct a fluidic diode.

Paricalcitol and Extended-Release Calcifediol for Treatment of Secondary Hyperparathyroidism in Non-Dialysis Chronic Kidney Disease: Results From a Network Meta-Analysis.

CONTEXT: Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) affecting mineral and bone metabolism and characterized by excessive parathyroid hormone (PTH) production and parathyroid hyperplasia. OBJECTIVE: The objective of this analysis was to compare the efficacy and adverse effects of extended-release calcifediol (ERC) and paricalcitol (PCT) by assessing their effect on the biomarkers PTH, calcium, and phosphate in patients with non-dialysis CKD (ND-CKD). METHODS: A systematic literature research was performed in PubMed to identify randomized control trials (RCTs). Quality assessment was done with the GRADE method. The effects of ERC vs PCT were compared using random effects in a frequentist setting. RESULTS: Nine RCTs comprising 1426 patients were included in the analyses. The analyses were performed on 2 overlapping networks, due to nonreporting of outcomes in some of the included studies. No head-to-head trials were identified. No statistically significant differences in PTH reduction were found between PCT and ERC. Treatment with PCT showed statistically significant increases in calcium compared with ERC (0.2 mg/dL increase; 95% CI, -0.37 to -0.05 mg/dL). No differences in effects on phosphate were observed. CONCLUSION: This network meta-analysis showed that ERC is comparable in lowering PTH levels vs PCT. ERC displayed avoidance of potentially clinically relevant increases in serum calcium, offering an effective and well-tolerated treatment option for the management of SHPT in patients with ND-CKD.

Patient preferences for characteristics differentiating ovarian stimulation treatments.

BACKGROUND: Little is known concerning patient preferences for IVF treatments. The objective of this study was to elicit patient preferences for characteristics differentiating ovarian stimulation treatments. METHODS: Women undergoing IVF were recruited from six clinics in Sweden between May 2010 and December 2010. Included patients completed a study questionnaire consisting of one contingent valuation (CV) question (with six different bids) and 16 conjoint analysis (CA) questions formulated as discrete choices between two hypothetical ovarian stimulation treatments (defined in terms of manufacturing method, method of administration, time required for administration, dose variability and hypothetical price). Patient preferences were derived using multinomial logit modelling. RESULTS: The final study population consisted of 294 women (mean age of 35). Respondents were willing to pay €360 [95% confidence interval (CI): €340-€390] to receive FSH derived from DNA technology instead of highly purified extract from urine from post-menopausal women, €300 (95% CI: €280-€320) to administer the FSH using a prefilled injection pen instead of a conventional syringe, €30 (95% CI: €20-€40) per saved minute required for administration and €530 (95% CI: €500-€570) to reduce the dose variability from 10-20% to 1-2% (P< 0.001 for all estimates). The result from the CV was similar to the CA. CONCLUSIONS: Women undergoing IVF place significant value on characteristics differentiating ovarian stimulation treatments. Product-specific aspects should be taken into account by decision-makers when discriminating between commercial gonadotrophins in clinical practice to align health-care decision-making with patient preferences and potentially improve the effectiveness of IVF interventions through enhanced patient satisfaction and treatment compliance. Preferences for treatment characteristics should also be considered in evaluations of ovarian stimulation products to capture their true value from a patient perspective.

Costs related to hip disease in patients eligible for total hip arthroplasty.

This study was designed to estimate direct and indirect costs incurred by hip disease in patients eligible for total hip arthroplasty (THA). Before THA, 2635 patients completed a questionnaire regarding the use of resources because of their hip disease. Costs were assigned using official statistical sources or market prices. Annual costs amounted to US$ 7666 per patient. In a regression analysis, higher annual costs were associated with working age, female gender, comorbidity, and operation waiting time more than 90 days (P < .005). The burden of disease for THA candidates is extensive, where loss of productivity is the principal cost. Long wait for surgery is associated with increased costs. This study provides baseline cost data, which will be useful for further health economic analyses and could provide guidance for health care decision makers.

High-Throughput Separation of Long DNA in Deterministic Lateral Displacement Arrays.

Length-based separation of DNA remains as relevant today as when gel electrophoresis was introduced almost 100 years ago. While new, long-read genomics technologies have revolutionised accessibility to powerful genomic data, the preparation of samples has not proceeded at the same pace, with sample preparation often constituting a considerable bottleneck, both in time and difficulty. Microfluidics holds great potential for automated, sample-to-answer analysis via the integration of preparatory and analytical steps, but for this to be fully realised, more versatile, powerful and integrable unit operations, such as separation, are essential. We demonstrate the displacement and separation of DNA with a throughput that is one to five orders of magnitude greater than other microfluidic techniques. Using a device with a small footprint (23 mm × 0.5 mm), and with feature sizes in the micrometre range, it is considerably easier to fabricate than parallelized nano-array-based approaches. We show the separation of 48.5 kbp and 166 kbp DNA strands achieving a significantly improved throughput of 760 ng/h, compared to previous work and the separation of low concentrations of 48.5 kbp DNA molecules from a massive background of sub 10 kbp fragments. We show that the extension of DNA molecules at high flow velocities, generally believed to make the length-based separation of long DNA difficult, does not place the ultimate limitation on our method. Instead, we explore the effects of polymer rotations and intermolecular interactions at extremely high DNA concentrations and postulate that these may have both negative and positive influences on the separation depending on the detailed experimental conditions.

Gastrointestinal tolerability and patterns of switching in patients treated for primary osteoporosis: the Swedish Adherence Register Analysis (SARA).

The objective of this study was to describe and analyze the gastrointestinal tolerability and medication switching in patients receiving treatment for primary osteoporosis in Sweden. The study was based on all patients starting therapy with alendronate, risedronate, strontium ranelate, and raloxifene in Sweden between 2005 and 2009. The primary outcome measure was start of treatment with a gastroprotective agent, and the secondary outcome was hospitalization for a gastrointestinal adverse event (GIAE). Switching was analyzed while patients were on treatment. The crude incidence of gastroprotective treatment during the first 6 months after initiation of osteoporosis therapy was 5.14%, 5.93%, 4.25%, and 2.86% for patients prescribed alendronate, risedronate, strontium ranelate, and raloxifene, respectively. Patients prescribed raloxifene had a significantly lower risk of filling a prescription for a gastroprotective agent compared with alendronate. There was no significant difference in the risk of hospitalization for GIAEs. Less than 3% switched therapy while on treatment. Patients prescribed risedronate, strontium ranelate, and raloxifene had a significantly higher risk of switching compared with patients taking alendronate. In conclusion, no significant difference in the incidence of GIAEs was found between patients prescribed alendronate, risedronate, and strontium ranelate. Individuals prescribed raloxifene had a significantly lower risk of GIAEs compared with patients prescribed alendronate. No significant difference was found in the frequency of hospitalization for GIAEs. Switching between osteoporosis medications and drug classes was uncommon. Prescribers should consider the real-world gastrointestinal safety of osteoporosis drugs when choosing between treatment options to potentially improve medication adherence and consequently effectiveness.

Risk of major osteoporotic fracture after first, second and third fracture in Swedish women aged 50 years and older.

BACKGROUND: Osteoporosis affects approximately one in five European women and leads to fragility fractures, which result in poor health, social and economic consequences. Fragility fractures are a strong risk factor for subsequent major osteoporotic fracture (MOF), with risk of MOF being elevated in the 1-2 years following an earlier fracture, a concept described as "imminent risk". This study examines risk of subsequent MOF in patients with one, two or three prior fractures by age and type of fracture. METHODS: In this retrospective, observational cohort study, Swedish women aged ≥50 years with ≥1 any clinical fragility fracture between July 1, 2006 and December 31, 2012 were identified from Sweden's National Patient Register. Each patient was age- and sex-matched to three controls without history of fracture. Group 1 women included those with one fragility fracture during the study period; Group 2 included those with two fragility fractures; and Group 3 included those with three fragility fractures. "Index fracture" was defined as the first fracture during the study period for Group 1; the second for Group 2; and the third for Group 3. Patients in each cohort and matched controls were followed for up to 60 months or until subsequent MOF (hip, vertebra, forearm, humerus), death or end of data availability. RESULTS: 231,769 women with at least one fracture were included in the study and therefore constituted Group 1; of these, 39,524 constituted Group 2 and of those, 7656 constituted Group 3. At five years, cumulative incidence of subsequent MOF was higher in patients with a history of fracture as compared to controls (Group 1: 20.7% vs 12.3%; Group 2: 32.0% vs 15.3%). Three-year cumulative incidence for Group 3 was 12.1% (vs 10.7% for controls). After adjusting for baseline covariates, risk of subsequent MOF was highest within 0-24 months following an index fracture, then decreased but remained elevated as compared to controls. Having two prior fractures, vertebral fractures and younger age at time of index fracture were associated with greater relative risk. CONCLUSIONS: Women with a history of osteoporotic fracture are at increased risk of subsequent fracture, which is highest during the first 24 months following a fracture. Younger women and those with vertebral fractures are at greatest relative risk, suggesting that treatment should target these patients and be timely enough to impact the period of imminent risk.

Differing impact of clinical factors on the risk of fracture in younger and older women in the general population and an osteoporosis clinic population.

This study assesses the impact of risk factors for fracture in women aged 80+ and 60-79. The results suggest that risk assessment which fits younger women may not be suited for the 80+ strata as many common risk factors are less predictive in the older compared to the younger cohort. PURPOSE: This study assesses whether the impact of classical risk factors for fracture due to osteoporosis is different in women aged 80+ and women aged 60-79. Since most prior research on the contribution of risk factors is based on patients below 80 years of age, this study aims to fill this knowledge gap to increase the accuracy of risk assessment in the oldest old. METHODS: Retrospective, observational cohort study using Swedish national health register data and BMD data from osteoporosis clinics. Women aged at least 60 were identified from a random sample of the general population and from the BMD databases and allocated to two populations representing patients at different stages of risk assessment. The relative impact of risk factors on fracture risk was assessed using multivariate competing risk regression with fracture as outcome and death as competing event. RESULTS: A total of 163,329 women were included from the general population (52,499 aged 80+) and 22,378 from the BMD databases (4563 aged 80+). The clinical risk factors with relatively highest effect on fracture risk in the older patients were prior fracture and hip T-score below - 2.5 SD. Other included risk factors showed lower impact in the older compared to the younger strata. CONCLUSIONS: This study confirms our understanding of the key risk factors for fracture: age, prior fracture, and a low T-score. Regarding remaining risk factors, risk assessment which fits younger women may not be suited for the 80+ strata as many common risk factors are less predictive in the older compared to the younger cohort.

Cost effectiveness of hormone therapy in women at high risks of fracture in Sweden, the US and the UK--results based on the Women's Health Initiative randomised controlled trial.

OBJECTIVE: The purpose of the study was to assess the cost effectiveness of hormone therapy (HT) for postmenopausal women without menopausal symptoms at an increased risk of fracture in Sweden, the UK and the US. METHODS: Using a state-transition model, the cost effectiveness of 50 year old women was assessed based on a societal perspective and the medical evidence found in the Women Health Initiative (WHI) trials. The model had a lifetime horizon divided into cycle lengths of 1 year and comprised the following disease states: hip fracture, vertebral fracture, wrist fracture, breast cancer, colorectal cancer, coronary heart disease, stroke and venous thromboembolic events. An intervention was modelled by its impact on the disease risks during and after the cessation of treatment. The model required data on clinical effects, risks, mortality rates, quality of life weights and costs valid for Sweden, the UK and the US. The main outcome of the model was cost per QALY gained of HT compared to no treatment. RESULTS: The results indicated that HT compared to no treatment was cost-effective for most sub-groups of hysterectomised women, whereas for women with an intact uterus without a previous fracture, HT was commonly dominated by no treatment. Fracture risks were the single most important determinant of the cost effectiveness results. CONCLUSIONS: HT is cost-effective in women with a hysterectomy irrespective of prior fracture status. In women with an intact uterus, opposed HT was cost-effective in those with a prior vertebral fracture, but cost-ineffective in women without a prior vertebral fracture. Even though HT is found cost-effective for a selection of osteoporotic women, it is unlikely to be considered for first-line therapy for osteoporosis because bisphosphonates have shown a similar reduction in fracture risks but without an increased risk of adverse events.

Long-term cost and effect on quality of life of osteoporosis-related fractures in Sweden.

BACKGROUND AND PURPOSE: Few economic or quality-of-life studies have investigated the long-term consequences of fragility fractures. This prospective observational data collection study assessed the cost and quality of life related to hip, vertebral, and wrist fracture 13-18 months after the fracture, based on 684 patients surviving 18 months after fracture. PATIENTS AND METHODS: Data regarding resource use and quality of life related to fractures was collected using questionnaires at 7 research centers in Sweden. Information was collected using patient records, register sources, and by asking the patient. Quality of life was estimated using the EQ-5D questionnaire. Direct and indirect costs were estimated from a societal standpoint. RESULTS: The mean fracture-related cost 13-18 months after a hip, vertebral, or wrist fracture were estimated to be euro2,422, euro3,628, and euro316, respectively. Between 12 and 18 months after hip, vertebral, and wrist fracture, utility increased by 0.03, 0.05, and 0.02, respectively. Compared to prefracture levels, the mean loss in quality of life between 13 and 18 months after fracture was estimated to be 0.05, 0.11, and 0.005 for hip, vertebral, and wrist fracture. INTERPRETATION: The sample of vertebral fracture patients was fairly small and included a high proportion of fractures leading to hospitalization, but the results indicate higher long-term costs and greater loss in quality of life related to vertebral fracture than previously believed.

The societal burden of osteoporosis in Sweden.

In osteoporosis, the bone mass is decreased, thereby increasing the risk of fractures. Common osteoporotic fractures include those at the hip, the spine and the forearm. Fractures are a burden to society; in terms of costs, morbidity and mortality. The main objective of this study was to estimate the burden of osteoporosis in Sweden. The study used a prevalence-based bottom-up approach to estimate the total annual burden of osteoporosis in Sweden. The burden was assessed from a societal perspective including medical care costs, non-medical care costs, informal care and indirect costs. Moreover, the value of quality-adjusted life-years (QALYs) lost because of fractures was included in the total burden estimations. The total annual fracture cost was estimated at MSEK 5639, which is about 3.2% of the total health care costs in Sweden. Community care was the most important cost category accounting for 66% of the total annual cost followed by medical care costs (31%), informal care (2%) and indirect costs (1%). By combining the annual value of QALYs lost (MSEK 10354) and the annual fracture costs, the total annual societal burden of osteoporosis in Sweden was estimated at MSEK 15183. Assuming no changes in the age-differentiated fracture risk, the annual burden of osteoporosis was projected to increase to MSEK 26301 in the year 2050. The present study shows the societal burden of osteoporosis in Sweden to be higher than previously perceived. This burden is substantial and must be acknowledged as an important health problem. Osteoporosis-related fractures do not only lead to high medical care costs but also to high community care costs.

The economic burden of depression in Sweden from 1997 to 2005.

BACKGROUND: Depression is one of the most common causes of disability and is associated with substantial reductions in the individual's quality of life. The aim of this study was to estimate the economic burden of depression to Swedish society from 1997 to 2005. MATERIALS AND METHODS: The study was conducted in a cost-of-illness framework, measuring both the direct cost of providing health care to depressive patients, and the indirect costs as the value of production that is lost due to morbidity or mortality. The costs were estimated by a prevalence and top-down approach. RESULTS: The cost of depression increased from a total of 1.7 billion euros in 1997 to 3.5 billion euros in 2005, representing a doubling of the burden of depression to society. The main reason for the cost increase is found in the significant increase in indirect costs due to sick leave and early retirement during the past decade, whereas direct costs were relatively stable over time. In 2005, indirect costs were estimated at 3 billion euros (86% of total costs) and direct costs at 500 million euros (16%). Cost of drugs was estimated at 100 million euros (3% of total cost). CONCLUSION: The cost of depression is substantial to society and the main cost driver is indirect costs due to sick leave and early retirement. The cost of depression has doubled during the past eight years making it a major public health concern for the individuals afflicted, carers and decision makers.

Exploring methods for comparing the real-world effectiveness of treatments for osteoporosis: adjusted direct comparisons versus using patients as their own control.

Using Swedish and Dutch registry data for women initiating bisphosphonates, we evaluated two methods of comparing the real-world effectiveness of osteoporosis treatments that attempt to adjust for differences in patient baseline characteristics. Each method has advantages and disadvantages; both are potential complements to clinical trial analyses. PURPOSE: We evaluated methods of comparing the real-world effectiveness of osteoporosis treatments that attempt to adjust for both observed and unobserved confounding. METHODS: Swedish and Dutch registry data for women initiating zoledronate or oral bisphosphonates (OBPs; alendronate/risedronate) were used; the primary outcome was fracture. In adjusted direct comparisons (ADCs), regression and matching techniques were used to account for baseline differences in known risk factors for fracture (e.g., age, previous fracture, comorbidities). In an own-control analysis (OCA), for each treatment, fracture incidence in the first 90 days following treatment initiation (the baseline risk period) was compared with fracture incidence in the 1-year period starting 91 days after treatment initiation (the treatment exposure period). RESULTS: In total, 1196 and 149 women initiating zoledronate and 14,764 and 25,058 initiating OBPs were eligible in the Swedish and Dutch registries, respectively. Owing to the small Dutch zoledronate sample, only the Swedish data were used to compare fracture incidences between treatment groups. ADCs showed a numerically higher fracture incidence in the zoledronate than in the OBPs group (hazard ratio 1.09-1.21; not statistically significant, p > 0.05). For both treatment groups, OCA showed a higher fracture incidence in the baseline risk period than in the treatment exposure period, indicating a treatment effect. OCA showed a similar or greater effect in the zoledronate group compared with the OBPs group. CONCLUSIONS: ADC and OCA each possesses advantages and disadvantages. Combining both methods may provide an estimate of real-world treatment efficacy that could potentially complement clinical trial findings.