Osteoporosis is a common complication of androgen deprivation therapy (ADT). In this large Swedish cohort study consisting of a total of nearly 180,000 older men, we found that those with prostate cancer and ADT have a significantly increased risk of future osteoporotic fractures. Androgen deprivation therapy (ADT) in patients with prostate cancer is associated to increased risk of fractures. In this study, we investigated the relationship between ADT in patients with prostate cancer and the risk of incident fractures and non-skeletal fall injuries both compared to those without ADT and compared to patients without prostate cancer. We included 179,744 men (79.1 ± 7.9 years (mean ± SD)) from the Swedish registry to which national directories were linked in order to study associations regarding fractures, fall injuries, morbidity, mortality and medications. We identified 159,662 men without prostate cancer, 6954 with prostate cancer and current ADT and 13,128 men with prostate cancer without ADT. During a follow-up of approximately 270,300 patient-years, we identified 10,916 incident fractures including 4860 hip fractures. In multivariable Cox regression analyses and compared to men without prostate cancer, those with prostate cancer and ADT had increased risk of any fracture (HR 95% CI 1.40 (1.28–1.53)), hip fracture (1.38 (1.20–1.58)) and MOF (1.44 (1.28–1.61)) but not of non-skeletal fall injury (1.01 (0.90–1.13)). Patients with prostate cancer without ADT did not have increased risk of any fracture (0.97 (0.90–1.05)), hip fracture (0.95 (0.84–1.07)), MOF (1.01 (0.92–1.12)) and had decreased risk of non-skeletal fall injury (0.84 (0.77–0.92)). Patients with prostate cancer and ADT is a fragile patient group with substantially increased risk of osteoporotic fractures both compared to patients without prostate cancer and compared to those with prostate cancer without ADT. We believe that this must be taken in consideration in all patients with prostate cancer already at the initiation of ADT.
Patients with primary hyperparathyroidism (pHPT) appear to have an increased risk of fractures and other comorbidities, such as cardiovascular disease, although results from previous studies have been inconsistent. Evidence of the association of parathyroidectomy (PTX) with these outcomes is also limited because of the lack of large well-controlled trials.
Objective
To investigate whether untreated pHPT was associated with an increased risk of incident fractures and cardiovascular events (CVEs) and whether PTX was associated with a reduced risk of these outcomes.
Design, Setting, and Participants
This cohort study included all patients who were diagnosed with pHPT at hospitals in Sweden between July 1, 2006, and December 31, 2017. Each patient was matched with 10 control individuals from the general population by sex, birth year, and county of residence. The patients were followed up until December 31, 2017. Data analyses were performed from October 2021 to April 2022.
Main Outcomes and Measures
The primary outcomes were fractures, CVEs, and death. Cumulative incidence of events was estimated using the 1-minus Kaplan-Meier estimator of corresponding survival function. Cox proportional hazards regression models were used to calculate hazard ratios (HRs).
Results
A total of 16 374 patients with pHPT were identified (mean [SD] age, 67.5 [12.9] years; 12 806 women [78.2%]), with 163 740 control individuals. The follow-up time was 42 310 person-years for the pHPT group and 803 522 person-years for the control group. Compared with the control group, the pHPT group had a higher risk of any fracture (unadjusted HR, 1.39; 95% CI, 1.31-1.48), hip fracture (unadjusted HR, 1.51; 95% CI, 1.35-1.70), CVEs (unadjusted HR, 1.45; 95% CI, 1.34-1.57), and death (unadjusted HR, 1.72; 95% CI, 1.65-1.80). In a time-dependent Poisson regression model, PTX was associated with a reduced risk of any fracture (HR, 0.83; 95% CI, 0.75-0.93), hip fracture (HR, 0.78; 95% CI, 0.61-0.98), CVEs (HR, 0.84; 95% CI, 0.73-0.97), and death (HR, 0.59; 95% CI, 0.53-0.65).
Conclusions and Relevance
Results of this study suggest that pHPT is associated with increased risk of fractures, CVEs, and death, highlighting the importance of identifying patients with this condition to prevent serious unfavorable outcomes. The reduced risk of these outcomes associated with PTX suggests a clinical benefit of surgery.
Previously undetected glucose abnormalities are common in patients with acute myocardial infarction (AMI). We evaluated long-term reliability of early glucometabolic classification of patients with AMI by repeated oral glucose tolerance tests (OGTTs).A glucometabolic OGTT-based classification was obtained in 122 patients by measuring capillary whole-blood glucose. The classification was performed on three occasions, before hospital discharge and 3 and 12 months thereafter.At discharge, 34, 31, and 34% were classified as having normal glucose tolerance, impaired glucose tolerance (IGT), or type 2 diabetes, respectively, and 93% of all patients with type 2 diabetes were still classified with type 2 diabetes (n = 27) or IGT (n = 12) after 12 months. The agreements between the OGTTs at discharge and 3 and 12 months were kappa = 0.35, P < 0.001, and kappa = 0.43, P < 0.001, respectively.The outcome of an OGTT performed in AMI patients at hospital discharge reliably informs on long-term glucometabolic state.
There are indications that the IGF system is related to both type 2 diabetes and cardiovascular disease (CVD). We tested the hypothesis that low IGF-I and high IGF-binding protein (IGFBP)-1 predict future cardiovascular mortality and morbidity in patients with acute myocardial infarction (AMI) and type 2 diabetes.The Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Trial recruited 1,253 patients with type 2 diabetes and AMI, of whom 575 were enrolled in a biochemical program with repeated blood sampling. Primary and secondary end points included adjudicated cardiovascular mortality and a composite of cardiovascular events (cardiovascular death, reinfarction, or stroke). Multiple Cox proportional hazard regression was used to study the relationship between the end points and the variables. Admission variables were used for the survival analysis and for blood glucose, and A1C updated mean values during follow-up were also available.During a median follow-up period of 2.2 years, 131 (23%) patients died from all-cause mortality and 102 (18%) from CVD, whereas 175 patients (30%) suffered from at least one cardiovascular event. The independent predictors for cardiovascular death in the Cox regression model were (as hazard ratio [HR] [95% CI]): ln updated mean blood glucose (12.2 [5.8-25.7]), age (+5 years) (1.5 [1.4-1.7]), ln IGFBP-1 (1.4 [1.1-1.8]), and ln serum creatinine at admission (2.4 [1.3-4.2]). The model predicting cardiovascular events contained the same variables (ln IGFBP-1 at admission, 1.2 [1.0-1.4]).High levels of IGFBP-1 at admission are associated with increased risk for cardiovascular mortality and morbidity in type 2 diabetes patients with AMI.
To investigate whether sitagliptin affects copeptin and osmolality, suggesting arginine vasopressin activation and a potential for fluid retention, compared with placebo, in patients with a recent acute coronary syndrome and newly discovered type 2 diabetes or impaired glucose tolerance. A second aim was to confirm whether copeptin correlated with insulin-like growth factor binding protein-1.Fasting blood samples were used from the BEta-cell function in Glucose abnormalities and Acute Myocardial Infarction trial, in which patients recently hospitalized due to acute coronary syndrome and with newly detected abnormal glucose tolerance were randomized to sitagliptin 100 mg once daily (n = 34) or placebo (n = 37). Copeptin, osmolality and insulin-like growth factor binding protein-1 were analysed at baseline and after 12 weeks.Copeptin and osmolality were unaffected by sitagliptin. There was no correlation between copeptin and insulin-like growth factor binding protein-1.Sitagliptin therapy does not appear to be related to activation of the arginine vasopressin system.
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