DXA assessment and fracture prevention in hormone positive breast cancer patients after treatment initiation with aromatase inhibitors: A registry-based cohort study.

Background: Several guidelines have been proposed to prevent aromatase inhibitors induced bone loss (AIBL), but there is scarce data on their endorsement in clinical practice. Aim: To assess bone health evaluation and fracture prevention in postmenopausal women with estrogen receptor (ER)-positive breast cancer after aromatase inhibitors (AI) initiation. Methods: An historical cohort analysis based on data from the cancer and osteoporosis Maccabi Health Services (MHS) registries from Jan 1st 2009 to Dec 31st 2020. Cases of estrogen receptor (ER)-positive breast cancer were extracted. Index date was set as the first aromatase inhibitors (AI) purchase. Variables such as age, BMI, smoking history, alcohol use, rheumatoid arthritis, diabetes, glucocorticosteroid use, previous fractures, BMD T-scores and purchases of AI and anti-resorptive agents were collected. Age under 50, previous cancer, prior major osteoporotic fractures and prior anti-resorptive treatment were exclusion criteria. Kaplan-Meier curves were generated to assess the time to outcomes. Multivariable Cox's proportional hazards survival model was performed. Results: A total of 8617 women initiating AI were eligible. The median follow up was 6.1 years. The mean (SD) age at index was 62.8 (9.2), the mean (SD) BMI was 29.1 (5.6). The mean (SD) T-score was -1.3 (1.2) at the lumbar spine, -1.5 (0.9) at the femoral neck and -1.0 (1.0) at the total hip. Twenty percent had type 2 diabetes, 8.1 % were active smokers, 3.8% had rheumatoid arthritis and 1.2% were exposed to glucocorticoids.A total of 37% and 53% underwent a DXA scan at 1 and 2 years from AI initiation, and 12% and 17% were prescribed an anti-resorptive agent at 1 and 2 years from index. Advanced age was associated with a higher rate of evaluation and treatment, while obesity and diabetes were associated with a lower rate. The cumulative incidence of a major osteoporotic fracture was 8.8 and 15.8 % at 5 and 10 years, respectively. Conclusions: Despite the excess risk of fractures, bone health assessment and preventive treatment are still partial and postponed in breast cancer AI treated patients. Strategies to ensure appropriate care are needed.

Identification and Characterization of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is characterized by substantial diagnostic and evaluation gaps with no systematic screening. Even recognized cases are undercoded because of the perceived benign nature of disease and current absence of approved pharmacologic treatment. NAFLD is often detected incidentally, particularly in the asymptomatic early phase. We doubled NAFLD detection via natural language processing of 1 million imaging reports combined with laboratory data from an unselected population. We describe NAFLD comorbidities and health care utilization as compared with age, sex, and body mass index matched control subjects.

Fracture incidence after denosumab discontinuation: Real-world data from a large healthcare provider.

BACKGROUND: Vertebral fractures (VF) upon Denosumab (DMAB) discontinuation were first described as a distinct phenomenon in 2015, yet the magnitude of this event remains undetermined. OBJECTIVES: To estimate fracture risk after DMAB discontinuation, in a real-world setting. METHODS: The computerized database of a 2.3-million members' state-mandated health organization was utilized to detect osteoporotic patients with at least two DMAB dispenses. Treatment discontinuation was defined as a refill gap of 3 months or more, while the discontinuation date was defined as an anticipated missed purchase date. Fractures were identified by an osteoporosis registry and individually adjudicated by an expert's review. Fractures occurring within one year from discontinuation among DMAB discontinuers (DD) and from the 2nd year of treatment onwards for persistent users (PU) were included. RESULTS: A total of 1500 DD (92% females, mean ±â€¯SD age = 71.8 ±â€¯9.5y), and 1610 PU (91%, 71.7 ±â€¯8.8) were identified. At baseline, the groups were comparable in fracture- history, bisphosphonate exposure, smoking, and bone density. Multiple VF occurred in 12 (0.8%) DD vs. 2 (0.1%) PU (p = 0.006). The overall rate of fractures per 100 patient-years of follow-up was significantly higher in DD than PU (RR 3.2, 95% CI 2.2-4.8), as well as the rate of VF (RR 4.7, 95% CI 2.3-9.6) and multiple VF (RR 14.6, 95% CI 3.3-65.3, effect size 1.06). CONCLUSIONS: Patients who discontinue DMAB are at greater risk of major OP fractures than those who persist with treatment. Same is true for clinical multiple vertebral fractures, yet the incidence of the latter was low. These findings demonstrate a need for greater awareness and thoughtful management of DMAB discontinuation.

The association between adherence with oral bisphosphonates and the risk of breast cancer in post-menopausal women.

BACKGROUND: Several observational studies have suggested a protective effect of oral bisphosphonates (BP) on the risk of breast cancer, but no such association has been seen in randomized control trials. The role of oral BP in breast cancer prevention remains unclear. AIM: To investigate the association between different levels of BP exposure and breast cancer incidence in a cohort of osteoporotic post-menopausal women. SUBJECTS AND METHODS: This historical prospective study was conducted using the computerized databases of Maccabi Healthcare Services (MHS) in Israel. Included in the study were osteopenic and osteoporotic women aged 55-75 years who started BP therapy between 1998 and 2012. The subjects were enrolled in MHS for at least 3 years before therapy initiation, and had a minimum follow-up of 5 years in MHS. Women with a previous cancer, and women treated with selective estrogen receptor modulators (SERMs) were excluded. BP exposure was expressed in quintiles of proportion of days covered (PDC) with BP during follow-up period and cancer incidence was ascertained by the Israel National Tumor Registry. Person-years of follow-up began on January 1st, 1998 and ended at the date of cancer diagnosis, death, or December 31st, 2012, whichever occurred first. RESULTS: A total of 11,717 patients (mean age = 66.87 ±â€¯4.38) were eligible for the analysis. During a total of 130,252 person-years of follow-up, (mean 7.2 years) 173 incident cases of breast cancer were diagnosed. Compared to women with a PDC with BP of 20% or lower, the adjusted hazard ratio for breast cancer were HR = 0.81 (95%CI: 0.48-1.39), HR = 0.82 (95%CI: 0.50-1.33), HR = 0.72 (95%CI:0.45-1.15) and HR = 1.14 (95%CI:0.76-1.70) among women with 20-40%, 40-60%, 60%-80%, and 80% or higher, PDC, respectively. CONCLUSION: In this study, we did not find a significant association between oral BP therapy for osteoporosis and the risk of breast cancer in postmenopausal women. The discrepancy between our results and the reports of such an association in observational studies might originate from an indication bias.

Exposure to alendronate is associated with a lower risk of bone metastases in osteoporotic women with early breast cancer.

BACKGROUND: Bisphosphonate (BP) treatment to prevent bone loss in breast cancer patients is already well established. However, data on the association between oral BP exposure before cancer diagnosis and disease outcomes in patients with early breast cancer are still scarce. Limited information is available on alendronate, the most common oral agent for the treatment of post-menopausal osteoporosis, regarding the association with bone metastases. AIM: To examine the association between oral bisphosphonate exposure before cancer diagnosis and the risk of bone metastases in osteoporotic women diagnosed with early breast cancer. SUBJECTS AND METHODS: This historical cohort study was conducted at the oncology division at Tel Aviv Medical Center. The study population included post-menopausal women with early breast cancer, diagnosed between 2002 and 2012. Data on cancer characteristics, diagnosis of osteoporosis, prior bisphosphonate exposure and outcome were collected from medical files. RESULTS: Among 297 osteoporotic women identified, 145 (49%) were treated with bisphosphonates (alendronate in 90% of the cases) before cancer diagnosis. BP-treated women were significantly older than the BP-naïve ones (67.9 years vs 64.6 years, p = 0.01), but comparable in risk factors and disease characteristics. Over a mean follow up of 5.6 years, nine cases of bone metastases were identified, eight of them among BP-naïve patient (cumulative incidence of 9.9%) and one among BP-treated patients (0.7%). In a multivariable Cox's proportional hazards survival model the use of BP prior to cancer diagnosis was associated with a hazard ratio of 0.04 (95%CI:0.004-0.403, p = 0.006) for bone metastasis. The HR remained similar after further adjustment for tumor stage and cancer therapy. CONCLUSIONS: History of alendronate use is associated with a lower likelihood of bone metastases in postmenopausal women with early breast cancer. Oral bisphosphonate treatment could be sufficient for reducing the risk of bone metastases.

Epidemiology and correlates of osteoporotic fractures among type 2 diabetic patients.

This study analyzed data on 87,224 osteoporotic patients with up to 18 years of computerized medical history. Patients with osteoporosis and type 2 diabetes had higher bone density yet more fractures than non-diabetic osteoporotic patients. Fracture incidence among the diabetic patients was associated with retinopathy and cardiovascular disease, but not with diabetes duration. PURPOSE: Little is known about the association between type 2 diabetes mellitus (T2DM) and fragility fractures or the mechanism(s) involved. We examined fracture correlates among T2DM patients with osteoporosis. METHODS: We used electronic health records of an osteoporosis (OP) registry cross-linked with a diabetes registry of a large payer provider healthcare organization in Israel. A cross-sectional analysis compared osteoporosis patients with and without T2DM, and a longitudinal Cox proportional hazard regression was used to identify incident fracture correlates. RESULTS: As of December 2015 a total of 87,224 current OP patients were identified, of whom 15,700 (18%) had T2DM. The T2DM OP patients were characterized by older age (mean 74.6 vs. 69.5), more males (20.3 vs. 14.0%), and a higher rate of chronic comorbidities compared to OP without diabetes. All major OP fractures (hip, spine, humerus, and forearm) were significantly more prevalent among T2DM OP patients (44 vs. 32%), with an overall age-standardized ratio of 1.22 (95% CI 1.19 to 1.25) and 1.15 (95% CI 1.10 to 1.21) for females and males respectively. The average T-scores were higher (femur neck - 1.8 vs. - 1.9, total hip - 1.2 vs. - 1.6, and vertebrae - 1.3 vs. - 1.7) for the T2DM OP patients compared to the non-T2DM OP patients. Among women with coexisting T2DM and osteoporosis (n = 10,812), fracture incidence was significantly associated with retinopathy (HR = 1.24, 95% CI 1.05 to 1.47) and cardiovascular disease (HR = 1.22, 95% CI 1.10 to 1.36) after controlling for age, bone mineral density T-score, rheumatoid arthritis, glucocorticoids, alcohol, and smoking). CONCLUSION: This large population-based study confirms the higher fracture risk of osteoporotic patients with T2DM, as compared to osteoporotic patients without T2DM, despite higher bone mineral density levels. The presence of micro- and macrovascular disease appears to increase this risk.

Development and validation of a predictive model for detection of colorectal cancer in primary care by analysis of complete blood counts: a binational retrospective study.

OBJECTIVE: The use of risk prediction models grows as electronic medical records become widely available. Here, we develop and validate a model to identify individuals at increased risk for colorectal cancer (CRC) by analyzing blood counts, age, and sex, then determine the model's value when used to supplement conventional screening. MATERIALS AND METHODS: Primary care data were collected from a cohort of 606 403 Israelis (of whom 3135 were diagnosed with CRC) and a case control UK dataset of 5061 CRC cases and 25 613 controls. The model was developed on 80% of the Israeli dataset and validated using the remaining Israeli and UK datasets. Performance was evaluated according to the area under the curve, specificity, and odds ratio at several working points. RESULTS: Using blood counts obtained 3-6 months before diagnosis, the area under the curve for detecting CRC was 0.82 ± 0.01 for the Israeli validation set. The specificity was 88 ± 2% in the Israeli validation set and 94 ± 1% in the UK dataset. Detecting 50% of CRC cases, the odds ratio was 26 ± 5 and 40 ± 6, respectively, for a false-positive rate of 0.5%. Specificity for 50% detection was 87 ± 2% a year before diagnosis and 85 ± 2% for localized cancers. When used in addition to the fecal occult blood test, our model enabled more than a 2-fold increase in CRC detection. DISCUSSION: Comparable results in 2 unrelated populations suggest that the model should generally apply to the detection of CRC in other groups. The model's performance is superior to current iron deficiency anemia management guidelines, and may help physicians to identify individuals requiring additional clinical evaluation. CONCLUSIONS: Our model may help to detect CRC earlier in clinical practice.

Statin use and the risk of age related macular degeneration in a large health organization in Israel.

OBJECTIVE: To investigate the association between persistent use of statins and the risk of age-related macular degeneration (AMD). DESIGN: A population-based retrospective cohort among adults who began statin therapy between 1998 and 2006 in a large health organization in Israel. The organization's central computerized databases were used to collect data on incident AMD cases diagnosed by ophthalmologists. RESULTS: A total of 108,973 individuals aged 55 or older were identified. During the study follow-up period 409,113 person-years, there were 2,732 incident AMD cases (6.68 per 1,000 person-years). The crude incidence density rate of AMD among patients at the lowest quintile of persistence with statins (7.18 per 1,000) was comparable to that of highest persistence quintile (7.13 per 1,000). After adjustment for potential confounders, patients in the highest quintile of persistence with statins had a hazard ratio of 0.99 (95% Confidence Interval: 0.78-1.26) for AMD compared with patients in the lowest proportion of days covered (PDC) quintile. In addition to age, AMD was found to associate with past smoking, asthma, diabetes and frequent visits to ophthalmologists or primary physicians prior to index date. CONCLUSIONS: Our study agrees with previous studies that showed no association between persistent use of statins and reduced risk of AMD. These results suggest that the early reports on a strong protective effect of statins against AMD development were probably a result of a small study effect.

Variations in hemoglobin before colorectal cancer diagnosis.

We have conducted the present case-control study to examine whether long-term variations in blood hemoglobin (Hb) levels within the normal range could detect subtle gastrointestinal bleeding in the early development of colorectal cancer (CRC). A total of 1074 CRC cases aged 45-75 years that have been diagnosed with CRC and had normal Hb levels were frequency matched for age and sex with cancer-free individuals at a ratio of 10 controls per case. Our retrospective analysis indicates that starting from 4 years prior to cancer diagnosis, a progressive significant (P<0.001) decrement in Hb levels (0.28 g/dl per 6 months) was found among cases but not among controls. CRC patients were characterized in an on-going, long-term, logarithmic decrement in Hb levels. Such small changes within the normal Hb range could be missed by health providers, but automatically detected by computerized alert algorithms..