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Background Bone metastases commonly occur in conjunction with solid tumors, and are associated with serious bone complications. Population-based estimates of bone metastasis incidence are limited, often based on autopsy data, and may not reflect current treatment patterns. Methods Electronic medical records (OSCER, Oncology Services Comprehensive Electronic Records, 569,000 patients, 52 US cancer centers) were used to identify patients ≥18 years with a solid tumor diagnosis recorded between 1/1/2004 and 12/31/2013, excluding patients with hematologic tumors or multiple primaries. Each patient’s index date was set to the date of his or her first solid tumor diagnosis in the selection period. Kaplan-Meier analyses were used to quantify the cumulative incidence of bone metastasis with follow-up for each patient from the index date to the earliest of the following events: last clinic visit in the OSCER database, occurrence of a new primary tumor or bone metastasis, end of study (12/31/2014). Incidence estimates and associated 95% confidence intervals (CI) are provided for up to 10 years of follow-up for all tumor types combined and stratified by tumor type and stage at diagnosis. Results Among 382,733 study patients (mean age 64 years; mean follow-up 940 days), breast (36%), lung (16), and colorectal (12%) tumors were most common. Mean time to bone metastasis was 400 days (1.1 years). Cumulative incidence of bone metastasis was 2.9% (2.9–3.0) at 30 days, 4.8% (4.7–4.8) at one year, 5.6% (5.5–5.6) at two years, 6.9% (6.8–7.0) at five years, and 8.4% (8.3–8.5) at ten years. Incidence varied substantially by tumor type with prostate cancer patients at highest risk (18% – 29%) followed by lung, renal or breast cancer. Cumulative incidence of bone metastasis increased by stage at diagnosis, with markedly higher incidence among patients diagnosed at Stage IV of whom11% had bone metastases diagnosed within 30 days. Conclusions These estimates of bone metastasis incidence represent the experience of a population with longer follow-up than previously published, and represent experience in the recent treatment landscape. Underestimation is possible given reliance on coded diagnoses but the clinical detail available in electronic medical records contributes to the accuracy of these estimates.

•In Sweden, giant cell tumor of the bone (GCTB) is a rare disease with an incidence of 1.2 per million population per year (1983–2011).•Primary malignant cases were uncommon (8%).•Peak incidence of GCTB was at age 20–39 years with a slight predominance in women.•Local recurrence rates in this current population-based series of GCTB remains high, overall for benign GCTB about 39%, and 75% for malignant GCTB.•The Swedish Cancer Registry is rare in providing population-based data on GCTB. Giant-cell tumor of bone (GCTB) is a locally aggressive histologically benign neoplasm with a less common malignant counterpart. Longitudinal data sources on GCTB are sparse, limited to single institution case series or surgical outcomes studies. The Swedish Cancer Registry is one of the few national population-based databases recording GCTB, representing a unique source to study GCTB epidemiology. We estimated incidence rate (IR) and overall mortality rates based on registry data. We identified patients with a GCTB diagnosis in the Swedish Cancer Registry from 1983 to 2011: benign (ICD-7 196.0–196.9; PAD 741) and malignant (PAD 746). Results were stratified by age at diagnosis, gender, and anatomical lesion location. The cohort included 337 GCTB cases (IR of 1.3 per million persons per year). The majority (n=310) had primary benign GCTB (IR of 1.2 per million per year). Median age at diagnosis was 34 years (range 10–88) with 54% (n=183) females. Malignant to benign ratio for women was 0.095 (16/167) and for men 0.077 (11/143). Incidence was highest in the 20–39 years age group (IR of 2.1 per million per year). The most common lesion sites were distal femur and proximal tibia. Mortality at 20 years from diagnosis was 14% (n=48) and was slightly higher for axial (17%; n=6) and pelvic (17%; n=4) lesions. Recurrence occurred in 39% of primary benign cases and 75% of primary malignant cases. In our modern population-based series primary malignant cases were uncommon (8%), peak incidence 20–39 years with slight predominance in women. Recurrence rates remain significant with overall 39% occurring in benign GCTB, and 75% in malignant form. The linkage between databases allowed the first population based estimates of the proportion of patients who received surgery at initial GCTB diagnosis, and those who also received subsequent surgeries.

ObjectivesRisk of infections in patients with solid cancers and bone metastases (BM) and the subsequent impact on prognosis is unclear. We examined the risk of infections among patients with cancer diagnosed with BM and the subsequent impact of infections on mortality.DesignPopulation-based cohort study.SettingDanish medical databases holding information on all hospital contacts in Denmark.ParticipantsAdult patients with solid cancers and BM between 1 January 1994 and 30 November 2013.Outcome measuresIn the risk analyses, the outcome was time to hospitalisation for common severe infections, pneumonia, sepsis and urinary tract infections. In the mortality analysis, we used Cox regression to compute HRs of death, modelling infection as time-varying exposure, stratifying for primary cancer type and adjusting for age, sex and comorbidities.ResultsAmong 23 336 patients with cancer and BM, cumulative incidences of common severe infections were 4.6%, 14.0% and 20.0% during 1 month, 1 year and 10 years follow-up. The highest incidence was observed for pneumonia, followed by urinary tract infections and sepsis. Infection was a strong predictor of 1 month mortality (adjusted HR: 2.1 (95% CI 1.8 to 2.3)) and HRs increased after 1 and 10 years: 2.4 (95% CI 2.3 to 2.6) and 2.4 (95% CI 2.4 to 2.6). Sepsis and pneumonia were the strongest predictors of death. Results were consistent across cancer types.ConclusionPatients with cancer and BM were at high risk of infections, which was associated with a more than twofold increased risk of death for up to 10 years of follow-up. The findings underscore the importance of preventing infections in patients with cancer and BM.

Osteoporosis and cardiovascular disease are common in older adults. Treatment of osteoporosis reduces the burden of debilitating fractures; however, it is important to understand the benefit versus risk of treatment. This study evaluates the risk of stroke (ischemic or hemorrhagic) and myocardial infarction (MI) among postmenopausal women and men initiating osteoporosis treatment with denosumab (receptor activator of nuclear factor κB ligand [RANKL] inhibitor) or zoledronic acid (bisphosphonate) between October 2010 and June 2019. A retrospective cohort study employing the new user/active comparator design was conducted. Analyses were conducted separately in two national US commercial databases, MarketScan® and Optum® for reproducibility. Inverse probability of treatment and censoring weighting was employed to control for confounding and informative censoring. Cumulative risks at 6‐month, 12‐month, and 36‐month time points were calculated and adjusted risk ratios and differences (with 95% confidence intervals [CIs]) were estimated. In MarketScan® and Optum® databases, 96,611 and 73,127 patients met all study eligibility criteria, respectively. At 36 months, the risk ratio estimates (zoledronic acid referent group) were 1.22 (95% CI, 0.77–1.66) and 0.97 (95% CI, 0.63–1.32) for MI and 1.00 (95% CI, 0.61–1.40) and 0.87 (95% CI, 0.56–1.17) for stroke in MarketScan and Optum, respectively. Most of the treatment associations across the other time periods and outcomes also had 95% CIs including the null value. In these large samples of real‐world US patients, no increased risk in MI and stroke were identified for up to 36 months of treatment in denosumab users compared with zoledronic acid users. © 2023 Amgen. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Introduction The incidence of cardiovascular events among cancer patients with bone metastases is poorly understood. We examined rates of cardiovascular events among cancer patients with bone metastases and mortality following such events. Methods Using Danish health registries, we identified all Danish cancer patients diagnosed with bone metastases (1994–2013) and followed them from bone metastasis diagnosis. We computed incidence rates (IR) per 100 person‐years and cumulative incidence for first‐time inpatient hospitalization or outpatient clinic visit for cardiovascular events, defined as myocardial infarction, ischemic stroke, or venous thromboembolism (VTE). We also analyzed all‐cause mortality rates including cardiovascular events as time‐varying exposure with adjustment for age, sex, and Charlson Comorbidity Index score. All analyses were performed overall and stratified by cancer type (prostate, breast, lung, and other). Results We included 23,113 cancer patients with bone metastases. The cumulative incidence of cardiovascular events was 1.3% at 30 days, 3.7% at 1 year, and 5.2% at 5 years of follow‐up. The highest IR was observed for VTE, followed by ischemic stroke and myocardial infarction, both overall and by cancer types. Lung cancer patients with bone metastases had the highest incidence of cardiovascular events followed by prostate and breast cancer. Occurrence of any cardiovascular event was a strong predictor of death (5 years following the event, the adjusted hazard ratio was 1.8 [95% confidence interval: 1.7–1.9]). Conclusion Cancer patients with bone metastases had a substantial risk of developing cardiovascular events, and these events were associated with a subsequent increased mortality. Our findings underscore the importance of continuous optimized prevention of and care for cardiovascular disease among cancer patients with bone metastases. Among 23,113 Danish cancer patients with bone metastases, 4% had developed cardiovascular disease within 1 year from diagnosis. Despite a high risk of cancer related death, cardiovascular disease was associated with a two‐fold increased risk of death.

Purpose Evaluation of drug safety during pregnancy is dependent on the number of exposed women during routine clinical practice with data available for analysis. We examined medication fills in pregnant and nonpregnant women within select disease cohorts: general population, migraine, diabetes, and hyperlipidemia to explore the potential use of claims data to assess medication use and safety during pregnancy. Methods This cohort study, using IBM MarketScan® Research Databases claims data, included women 10–54 years of age with pregnancy resulting in a liveborn infant between January 2010 and September 2015 and matched nonpregnant women. Medication use (antidepressants, antihypertensives, sedatives, glucose-lowering medications, antiepileptics, antipsychotics, lipid-lowering medications) was abstracted from pharmacy claims 180 days before last menstrual period through 180 days postdelivery. Results Among 753,760 women in the general pregnancy population (including 73,268 migraine, 50,155 hyperlipidemia, and 8361 diabetes; non-exclusive cohorts), antidepressants, antihypertensives, and sedatives were the most commonly used medications during pregnancy. Medications of interest were less commonly used in the pregnancy cohort than in the matched nonpregnant cohort within each time period (e.g., 3.7% vs 13.1% antidepressant use in 1st trimester). Most prescription fills were less common during pregnancy then pre-pregnancy. Post-pregnancy, prescription fills increased to or exceeded pre-pregnancy levels, except antihypertensive and glucose-lowering medications, which increased during pregnancy. Conclusions Medication use among pregnant women was low and different from that among matched nonpregnant women. The underlying size of large commercial claims databases offer opportunities for efficient evaluation of potential safety concerns, particularly for rare drug exposures, compared to traditional pregnancy registries.

Purpose This study examined real-world long-term use of guideline-recommended bone targeted agents (BTA) among patients with metastatic solid tumors. Methods Adults with a solid tumor diagnosis followed by a bone metastasis diagnosis in 2012–2014 were identified from electronic medical records in the Oncology Services Comprehensive Electronic Records (OSCER) database. Patients initiated zoledronic acid (ZA) or denosumab on or after the bone metastasis diagnosis and were followed through last clinic visit by 30 June 2015. We describe time to BTA initiation, compliance (≥12 administrations in a year), switching, and non-persistence (switch or ≥90 day gap in therapy), by agent and follow-up period. Results The majority of the 14,881 study patients (50% female, 65% age ≥65 years) had breast (33%), prostate (26%), or lung (26%) tumors. Half of all patients initiated on each agent, with denosumab initiations exceeding ZA initiations in 2014. Most (91% denosumab, 93% ZA) initiations occurred within 3 months of bone metastasis diagnosis. At 1, 2, and 3 years post-initiation, denosumab patients were less likely to switch agents (4, 3, and 1% versus 14, 12, and 11%) and more likely to be compliant (50, 37, and 31% versus 41, 26, and 6%). Median time to non-persistence was 25.9 months for denosumab and 17.2 months for ZA, p  < 0.0001. Conclusions This is the first study reporting long-term treatment patterns for the two primary BTAs used in the USA. The greater compliance and longer persistence observed among denosumab patients may improve treatment effectiveness achieved in the real-world setting.

Current information on the incidence and prevalence of bone metastases in women with breast cancer is scarce. This study examined the occurrence and predictors of bone metastases, as well as post-metastasis survival in a prospective cohort of Canadian women with breast cancer. We included women treated for early-stage (stage I, II, or III) breast cancer at the Henrietta Banting Breast Centre (HBBC) in Toronto, Canada between 1987 and 2000. Data were abstracted from medical records and pathology reports in the HBBC database; follow-up extended to end of data availability or August 31, 2015. Actuarial survival analyses provided cumulative incidence of bone metastases at 5, 10, and 15 years after breast cancer diagnosis. Kaplan–Meier curves describe breast cancer mortality. Regression models assessed patient, tumor, and treatment characteristics as predictors of bone metastases with all-cause mortality as a competing risk. Among 2097 women studied, the 5-, 10-, and 15-year probability of bone metastasis was 6.5, 10.3, and 11.3 % for the first recurrence, and 8.4, 12.5, and 13.6 % for any bone recurrence. At median follow-up (12.5 years), 13.2 % of patients had bone metastases. Median survival was 1.6 years following bone metastasis, and shorter if both bone and visceral metastases occurred. Advanced age and adjuvant treatment with tamoxifen were protective against bone metastasis. In this representative cohort of women diagnosed with early-stage breast cancer in Ontario, Canada, with long follow-up, the incidence of bone metastases was consistent with longitudinal studies from the United Kingdom, Denmark, and the US.

Objective To compare the risk of non-fatal venous thromboembolism in women receiving oral contraceptives containing drospirenone with that in women receiving oral contraceptives containing levonorgestrel.Design Nested case-control and cohort study.Setting The study was based on information from PharMetrics, a United States based company that collects information on claims paid by managed care plans.Participants The study encompassed all women aged 15 to 44 years who received an oral contraceptive containing either drospirenone or levonorgestrel after 1 January 2002. Cases were women with current use of a study oral contraceptive and a diagnosis of venous thromboembolism in the absence of identifiable clinical risk factors (idiopathic venous thromboembolism). Up to four controls were matched to each case by age and calendar time.Main outcome measures Odds ratios comparing the risk of non-fatal venous thromboembolism in users of the two contraceptives; incidence rates and rate ratios of non-fatal venous thromboembolism for users of each of the study contraceptives.Results 186 newly diagnosed, idiopathic cases of venous thromboembolism were identified in the study population and matched with 681 controls. In the case-control analysis, the conditional odds ratio for venous thromboembolism comparing use of oral contraceptives containing drospirenone with use of those containing levonorgestrel was 2.3 (95% confidence interval 1.6 to 3.2). The incidence rates for venous thromboembolism in the study population were 30.8 (95% confidence interval 25.6 to 36.8) per 100 000 woman years among users of oral contraceptives containing drospirenone and 12.5 (9.61 to 15.9) per 100 000 woman years among users of oral contraceptives containing levonorgestrel. The age adjusted incidence rate ratio for venous thromboembolism for current use of oral contraceptives containing drospirenone compared with those containing levonorgestrel was 2.8 (2.1 to 3.8).Conclusions The risk of non-fatal venous thromboembolism among users of oral contraceptives containing drospirenone seems to be around twice that of users of oral contraceptives containing levonorgestrel, after the effects of potential confounders and prescribing biases have been taken into account.

Observational postapproval safety studies are needed to inform medication safety during pregnancy. Real-world databases can be valuable for supporting such research, but fitness for regulatory purpose must first be vetted. Here, we demonstrate a fit-for-purpose assessment of the Japan Medical Data Center (JMDC) claims database for pregnancy safety regulatory decision-making. The Duke-Margolis framework considers a database's fitness for regulatory purpose based on relevancy (capacity to answer the research question based on variable availability and a sufficiently sized, representative population) and quality (ability to validly answer the research question based on data completeness and accuracy). To assess these considerations, we examined descriptive characteristics of infants and pregnancies among females ages 12-55 years in the JMDC between January 2005 and March 2022. For relevancy, we determined that critical data fields (maternal medications, infant major congenital malformations, covariates) are available. Family identification codes permitted linkage of 385,295 total mother-infant pairs, 57% of which were continuously enrolled during pregnancy. The prevalence of specific congenital malformation subcategories and maternal medical conditions were representative of the general population, but preterm births were below expectations (3.6% versus 5.6%) in this population. For quality, our methods are expected to accurately identify the complete set of mothers and infants with a shared health insurance plan. However, validity of gestational age information was limited given the high proportion (60%) of missing live birth delivery codes coupled with suppression of infant birth dates and inaccessibility of disease codes with gestational week information. The JMDC may be well suited for descriptive studies of pregnant people in Japan (eg, comorbidities, medication usage). More work is needed to identify a method to assign pregnancy onset and delivery dates so that in utero medication exposure windows can be defined more precisely as needed for many regulatory postapproval pregnancy safety studies.