吸入糖皮质激素对女性哮喘患者骨密度和骨代谢的影响

背景吸入性糖皮质激素是治疗哮喘的一线药物.但长期吸入大剂量糖皮质激素是否有引起骨质丢失的危险尚不能排除,尤其对女性哮喘患者.目的了解国内女性哮喘患者长期吸入糖皮质激素是否会对骨密度和骨代谢产生影响.设计以患者为观察对象,配对比较分析.对象纳入40例女性哮喘患者为1998-02/2002-02在南京医科大学第一附属医院呼吸科门诊就诊者.均无长期全身使用激素史,且对实验目的知情同意.其中吸入糖皮质激素组(吸入组)20例每日坚持吸入激素≥5个月(年龄18～63岁,绝经5例),对照组20例(年龄18～60岁,绝经5例)采用常规平喘解痉药物治疗.对照组按年龄、性别和绝经情况与吸入组配对,平均人).方法采用双能X线骨密度仪测定患者L2-4椎体、股骨颈、股骨转子、股骨三角及股骨总量的骨密度,以绝对值和T评分(即与同性别成年人骨峰值相比的标准差)表示.同时与其同年龄、性别相应正常数据相比较,确定骨密度在这些部位的相对值.同时用放射免疫分析法等测定这些患者的血骨钙素以及碱性磷酸酶等指标,进行对比分析.主要观察指标①两组患者骨密度比较.②两组血骨钙素以及碱性磷酸酶等指标比较.③吸入组日均吸入激素剂量和吸入激素的累积量与骨密度的相关性.结果两组患者L2-4椎体、股骨颈、股骨转子、股骨三角及股骨总量的骨密度值及T评分差异不明显(P＞0.05).吸入组20例患者的上述5个部位骨密度值与其相应日均吸入糖皮质激素剂量之间无明显相关性(r=-0.325～-0.110 2,P＞0.05);L2-4椎体、股骨颈和股骨三角的骨密度值与吸入糖皮质激素累积量之间呈显著负相关(r=-0.495,-0.517,-0.531,P＜0.05).吸入组患者上述5个部位骨密度的T评分与其吸入糖皮质激素累积量无明显相关性(r=0.443～0.295,P＞0.05).吸入组股骨三角处的绝对骨密度值与其年龄呈显著负相关(r=-0.506,P＜0.05),而对照组5个部位绝对骨密度值与其年龄之间无明显相关性(r=-0.079～0.326,P＞0.05).两组血清骨钙素及其他生化指标差异不明显(P＞0.05).结论长期吸入糖皮质激素控制哮喘,对女性哮喘患者的骨密度和骨代谢一般不会产生明显影响,但长期吸入激素的女性哮喘患者随着吸入激素累积量的增加和或年龄的增长,引起骨质丢失的危险可能会增高.

Influence of inhaled glucocorticoids on bone mineral density and bone metabolism in asthmatic women

BACKGROUND: Inhaled glucocorticoids(IGC) are powerful anti_inflammatory agents used in the treatment of asthma. But it is still uncertain whether long-term use of the IGC affects bone metabolism in asthmatic patients, especially women.OBJECTIVE: To investigate if the prolonged treatment with IGC to Chinese asthmatic woman has a detrimental effect on bone mass and metabolism.DESIGN: A matched controlled study based on the patients SETTING:Clinical Laboratory and the Department of Respiratory Medicine, First Affiliated Hospital, Nanjing Medical University.PARTICIPANTS: From February 1998 to February 2002, forty female Chinese patients with bronchial asthma, regularly followed up at our outpatient clinic, all in the Nanjing area, none of them having a history of chronic systemic GC use, agreed to take part in the study, were selected and divided into two groups: therapeutic group (IGC group): 20 asthmatic women, aged 18-63 years, 5 menopausals, received IGC therapy regularly for at least 5 months; Control group: 20 asthmatic women, aged 18-60 years, 5 menopausals, never received IGC received conventional bronchodilators . They were matched individually for sex, age and menopausal status.METHODS: Bone mineral density (BMD) at the lumbar spine (2-4),femoral neck, trochanter, ward's triangle and total body of femur were measured by dual energy X-ray absorptiometry, BMD were expressed as a absolute value and a T score considered as a SD from peak bone mass respectively. Meanwhile, BMD was also expressed as a percentage (%), which was defined by comparing the BMD absolute value of subjects and BMD normal value of isosexual age cohorts. Osteocalcin and some other markers of bone metabolism were measured by radio immunoassay in two groups.daily dose and accumulative total dose of IGC and BMD in the IGC group.RESULTS: There were no significant difference between two groups in BMD and T score (including the lumbar spine (2-4), femoral neck,trochanter, ward' s triangle and total body of femur) (P ＞ 0.05). There were also no significant correlation between daily dose of IGC and BMD of above 5 parts in the IGC group (r=-0.325 to -0.1102, P ＞ 0.05). But,there were significantly negative correlation between the accumulative total dose of IGC and BMD at lumbar spine2-4,femoral neck and ward's triangle(r=-0.495 ,-0.517,-0.531 ,P ＜ 0.05).There were no significant correlation between the accumulative total dose of IGC and T score of above 5 parts in the IGC group (r=0.443to 0.295 ,P ＞ 0.05). There was negative correlation between the age and the BMD at ward's triangle in the IGC group(r=-0.506,P ＜ 0.05). However ,BMD at 5 locus were not correlated with the age in control group (r=-0.079 to 0.326, P ＞ 0.05).Osteocalcin and some other markers of bone metabolism were no significant difference between two groups (P ＞ 0.05).CONCLUSION: The data suggests that there is no significant influence of IGC on bone mineral density and bone metabolism in asthmatic women,but if continuing exposures to high doses over many years,there may be a detrimental effect on bone mass and metabolism in women, especially elder or postmenopausal asthmatic women treated with IGC who may be more susceptible to any bone mineral loss caused by IGC.