Tauchmanova L, Guerra E, Pivonello R, De Martino M C, De Leo M, Caggiano F, Lombardi G, Colao A
Department of Molecular and Clinical Endocrinology and Oncology, Federico II University of Naples, Naples, Italy.
J Endocrinol Invest. 2009 May;32(5):390-4. doi: 10.1007/BF03346473.
Chronic mild endogenous glucocorticoid excess has been shown to cause bone loss and to increase fracture risk in both post-menopausal and premenopausal women. Currently, it is unclear if patients with subclinical Cushing's syndrome (SCS) with osteoporosis or osteopenia may benefit from antiresorptive treatment and the type of therapy to be given.
This pilot randomized study was aimed at evaluating the effects of 12-month im administration of clodronate (100 mg every week) on vertebral and femoral bone mineral density (BMD), bone turnover markers and on subjective pain in premenopausal women with SCS due to adrenal incidentalomas.
Forty-six women (age, 43.1+/-7.7 yr) with SCS due to adrenal incidentaloma and osteoporosis/osteopenia were randomized to receive clodronate plus supplement of Calcium (500 mg daily) and Vitamin D3 (800 mg daily) (group 1, no.=23) or supplements only (group 2, no.=23). Both groups were similar in terms of age, body mass index, cortisol levels, BMD values, and bone turnover markers. All of the women were re-evaluated after 12 months.
After 12 months of treatment, in group 1, a significant increase in lumbar BMD occurred (p=0.04), while bone turnover markers decreased by about one third (p<0.05). In group 2, bone turnover markers did not change and BMD values slightly decreased (p=ns). The differences in bone turnover markers and in lumbar BMD between the two groups were significant (p<0.05, all). No new vertebral fracture occurred in group 1, while in group 2 the spine radiographies revealed 2 new fractures and a worsening of two pre-existent fractures. An improvement in subjective back pain, assessed by visual analogue scale pain score was observed in group 1 (from 4.3+/-2.7 to 2.9+/-2.0; p<0.05) but not in group 2 (from 4.4+/-3.1 to 4.2+/-3.4; p=ns). No significant changes occurred in cortisol secretion or clinical picture of the SCS during the study.
Intramuscular administration of clodronate effectively increased lumbar BMD values, preserved bone mass at the femoral neck, stabilized vertebral fracture index, and decreased subjective back pain in pre-menopausal women with SCS. Since the untreated group continued to lose bone, antiresorptive treatment should be considered in patients with SCS, according to the prevision of surgical treatment, prevalent fractures, BMD values, age, concomitant morbidities, and desire for pregnancy.
慢性轻度内源性糖皮质激素过多已被证明会导致绝经后和绝经前女性骨质流失并增加骨折风险。目前，尚不清楚患有骨质疏松或骨质减少的亚临床库欣综合征（SCS）患者是否能从抗吸收治疗中获益以及应给予何种类型的治疗。
这项初步随机研究旨在评估每周一次肌肉注射氯膦酸盐（100毫克），持续12个月，对因肾上腺偶发瘤导致SCS的绝经前女性的椎体和股骨骨密度（BMD）、骨转换标志物及主观疼痛的影响。
46名因肾上腺偶发瘤导致SCS且患有骨质疏松/骨质减少的女性（年龄43.1±7.7岁）被随机分为两组，一组接受氯膦酸盐加钙补充剂（每日500毫克）和维生素D3补充剂（每日800毫克）（第1组，n = 23），另一组仅接受补充剂（第2组，n = 23）。两组在年龄、体重指数、皮质醇水平、BMD值和骨转换标志物方面相似。所有女性在12个月后重新进行评估。
治疗12个月后，第1组腰椎BMD显著增加（p = 0.04），而骨转换标志物下降约三分之一（p < 0.05）。第2组骨转换标志物未变化，BMD值略有下降（p =无统计学意义）。两组之间骨转换标志物和腰椎BMD的差异具有统计学意义（p < 0.05，均如此）。第1组未发生新的椎体骨折，而第2组脊柱X线片显示有2例新骨折以及2例原有骨折病情恶化。通过视觉模拟评分法疼痛评分评估，第1组主观背痛有所改善（从4.3±2.7降至2.9±2.0；p < 0.05），而第2组未改善（从4.4±3.1降至4.2±3.4；p =无统计学意义）。研究期间SCS的皮质醇分泌或临床表现无显著变化。
肌肉注射氯膦酸盐可有效增加绝经前SCS女性的腰椎BMD值，维持股骨颈骨量，稳定椎体骨折指数，并减轻主观背痛。由于未治疗组持续骨质流失，应根据手术治疗预期、既往骨折情况、BMD值、年龄、合并症及妊娠意愿等因素，考虑对SCS患者进行抗吸收治疗。
