RESUMEN
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. INTRODUCTION: 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. METHODS: 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. RESULTS: 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)). CONCLUSIONS: 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.
Asunto(s)
Antagonistas de Andrógenos/efectos adversos , Antineoplásicos Hormonales/efectos adversos , Fracturas Osteoporóticas/inducido químicamente , Neoplasias de la Próstata/tratamiento farmacológico , Accidentes por Caídas/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Comorbilidad , Estudios de Seguimiento , Fracturas de Cadera/inducido químicamente , Fracturas de Cadera/epidemiología , Humanos , Incidencia , Masculino , Fracturas Osteoporóticas/epidemiología , Neoplasias de la Próstata/epidemiología , Sistema de Registros , Factores de Riesgo , Suecia/epidemiologíaRESUMEN
BACKGROUND: There is high evidence for secondary prevention of fractures, including hip fracture, with alendronate treatment, but alendronate's efficacy to prevent hip fractures in the oldest-old (≥80 years old), the population with the highest fracture risk, has not been studied. OBJECTIVE: To investigate whether alendronate treatment amongst the oldest-old with prior fracture was related to decreased hip fracture rate and sustained safety. METHODS: Using a national database of men and women undergoing a fall risk assessment at a Swedish healthcare facility, we identified 90 795 patients who were 80 years or older and had a prior fracture. Propensity score matching (four to one) was then used to identify 7844 controls to 1961 alendronate-treated patients. The risk of incident hip fracture was investigated with Cox models and the interaction between age and treatment was investigated using an interaction term. RESULTS: The case and control groups were well balanced in regard to age, sex, anthropometrics and comorbidity. Alendronate treatment was associated with a decreased risk of hip fracture in crude (hazard ratio (HR) 0.62 (0.49-0.79), P < 0.001) and multivariable models (HR 0.66 (0.51-0.86), P < 0.01). Alendronate was related to reduced mortality risk (HR 0.88 (0.82-0.95) but increased risk of mild upper gastrointestinal symptoms (UGI) (HR 1.58 (1.12-2.24). The alendronate association did not change with age for hip fractures or mild UGI. CONCLUSION: In old patients with prior fracture, alendronate treatment reduces the risk of hip fracture with sustained safety, indicating that this treatment should be considered in these high-risk patients.
Asunto(s)
Alendronato/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Fracturas Osteoporóticas/prevención & control , Anciano de 80 o más Años , Índice de Masa Corporal , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Fracturas de Cadera/prevención & control , Humanos , Masculino , Recurrencia , Medición de Riesgo , Factores de Riesgo , Suecia , Resultado del TratamientoAsunto(s)
Alcohol Deshidrogenasa/química , Bases de Datos Factuales , Hidroxiesteroide Deshidrogenasas/química , 11-beta-Hidroxiesteroide Deshidrogenasas , Alcohol Deshidrogenasa/metabolismo , Biología Computacional , Evolución Molecular , Humanos , Modelos Moleculares , Conformación Proteica , Ácido Ursodesoxicólico/metabolismoRESUMEN
The role of calcium as a regulator for neuronal function is very important. Calcium initiates many reactions that determine the behavior of the neuronal cell. In this article we use a kinetic model of the presynaptic synapsin I protein. This protein is responsible, via phosphorylation, for regulating the amount of transmitter vesicles available for release. This protein has been shown to inhibit the amount of vesicles ready for release in its dephosphorylated state, and releases its inhibitory binding due to phosphorylation. The phosphorylation of synapsin I depends on cyclic adenosine monophosphate and type II calcium/calmodulin protein kinase. Due to the duration of these two second messengers, we show that short-term facilitation does not have to depend on calcium residues. Furthermore, we show that calcium residues (in parts of microM range) promote increased facilitation due to the additional calcium reacting with the second messenger system.