Nurmi-Lüthje Ilona, Lüthje Peter, Kaukonen Juha-Pekka, Kataja Matti, Kuurne Salla, Naboulsi Helena, Karjalainen Kalevi
Department of Public Health, University of Helsinki, Helsinki, Finland.
Drugs Aging. 2009;26(5):409-21. doi: 10.2165/00002512-200926050-00005.
Several studies have shown excess mortality among hip fracture patients compared with the normal population of the same age. Finnish guidelines for medical treatment of hip fracture patients recommend anti-osteoporosis medication and the daily concomitant use of prescribed calcium and vitamin D supplements. However, whether post-fracture use of calcium and vitamin D supplements is associated with survival in such patients has not been evaluated.
To study the association between survival in hip fracture patients and patients' sex and age, pre-fracture vitamin D status, American Society of Anesthesiologists - Physical Status (ASA-PS) class, type of fracture and post-fracture use of prescribed calcium plus vitamin D and anti-osteoporotic medication.
The study population was 221 hip fracture patients primarily treated in acute care for a new hip fracture in 2003-4 in two Finnish hospitals. After a median of 27.5 months from the fracture, a questionnaire was sent to all patients who were still alive at the time (n = 137). The patients were queried about their use of prescribed calcium plus vitamin D supplementation and of anti-osteoporotic drugs. The follow-up time for use of anti-osteoporotic medication and prescribed calcium and vitamin D was 19.5-36 months (median 27.5 months). Data on the use of prescribed calcium plus vitamin D supplementation and anti-osteoporotic drugs were checked against information on reimbursement of drug prescriptions held by the Finnish Social Insurance Institution. A total of 4 years' (48 months') survival data for all patients in the study population was also obtained, with the dates of patient deaths being checked against Official National and Regional population statistics. Patient survival was analysed using both the Bayesian multivariate analysis and the life table method.
In the multivariate analysis, the combination of variables that best explained post-fracture survival was as follows: age <80 years; ASA-PS class 1-2 (ASA-PS class 1 and 2 data were combined in calculations); post-fracture use of prescribed calcium plus vitamin D supplements concomitantly with anti-osteoporotic drugs; post-fracture use of prescribed calcium plus vitamin D supplements; post-fracture use of anti-osteoporotic drugs only; and type of fracture (femoral neck or subtrochanteric). This model correctly predicted 74% of cases. At 36 months, we observed a 36% reduction in deaths in females who used prescribed calcium plus vitamin D supplementation and a corresponding 43% reduction in males. Survival of females who used anti-osteoporotic drugs concomitantly was even greater (43% reduction in deaths) over the entire follow-up period. Excess mortality was highest in females and males who used neither anti-osteoporotic drugs nor prescribed calcium and vitamin D.
Our results indicate a potential relationship between reduced mortality and post-fracture use of prescribed calcium plus vitamin D supplementation and, in females, concomitant use of anti-osteoporotic drugs. However, further investigations are needed to understand the reason for the reduction in the risk of death. Population-based, randomized, placebo-controlled trials with total mortality as the main endpoint should be conducted to verify our results.
多项研究表明,与同龄正常人群相比,髋部骨折患者的死亡率更高。芬兰髋部骨折患者的医学治疗指南推荐使用抗骨质疏松药物,并每日同时服用规定剂量的钙和维生素D补充剂。然而,骨折后使用钙和维生素D补充剂是否与这类患者的生存率相关尚未得到评估。
研究髋部骨折患者的生存率与患者的性别、年龄、骨折前维生素D状态、美国麻醉医师协会身体状况分级(ASA-PS分级)、骨折类型以及骨折后使用规定剂量的钙加维生素D和抗骨质疏松药物之间的关联。
研究对象为2003年至2004年在芬兰两家医院因新发髋部骨折接受急性治疗的221例髋部骨折患者。在骨折后中位时间27.5个月时,向当时仍存活的所有患者(n = 137)发送了一份问卷。询问患者使用规定剂量的钙加维生素D补充剂和抗骨质疏松药物的情况。抗骨质疏松药物以及规定剂量的钙和维生素D的随访时间为19.5至36个月(中位时间27.5个月)。将规定剂量的钙加维生素D补充剂和抗骨质疏松药物的使用数据与芬兰社会保险机构持有的药物处方报销信息进行核对。还获取了研究人群中所有患者的4年(48个月)生存数据,并将患者死亡日期与国家和地区官方人口统计数据进行核对。使用贝叶斯多变量分析和生命表法对患者生存率进行分析。
在多变量分析中,最能解释骨折后生存率的变量组合如下:年龄<80岁;ASA-PS分级为1-2级(计算时将ASA-PS 1级和2级数据合并);骨折后同时使用规定剂量的钙加维生素D补充剂和抗骨质疏松药物;骨折后使用规定剂量的钙加维生素D补充剂;骨折后仅使用抗骨质疏松药物;以及骨折类型(股骨颈或转子下)。该模型正确预测了74%的病例。在36个月时,我们观察到使用规定剂量的钙加维生素D补充剂的女性死亡人数减少了36%,男性相应减少了43%。在整个随访期间,同时使用抗骨质疏松药物的女性生存率更高(死亡人数减少43%)。既不使用抗骨质疏松药物也不使用规定剂量的钙和维生素D的女性和男性的超额死亡率最高。
我们的结果表明,骨折后使用规定剂量的钙加维生素D补充剂与死亡率降低之间可能存在关联,在女性中,同时使用抗骨质疏松药物也与死亡率降低有关。然而,需要进一步研究以了解死亡风险降低的原因。应以总死亡率为主要终点进行基于人群的随机安慰剂对照试验,以验证我们的结果。