Tsai Joy N, Jiang Linda A, Lee Hang, Hans Didier, Leder Benjamin Z
Endocrine Unit, Massachusetts General Hospital, Boston, MA, USA.
Endocrine Unit, Massachusetts General Hospital, Boston, MA, USA.
J Clin Densitom. 2017 Oct-Dec;20(4):507-512. doi: 10.1016/j.jocd.2017.05.007. Epub 2017 Jun 16.
In postmenopausal women, 2 yr of combined teriparatide and denosumab increases bone mineral density more than either drug alone, and switching from either combination or teriparatide to denosumab for an additional 2 yr further increases bone mineral density. Conversely, switching from denosumab to teriparatide results in transient bone loss. The effects of these interventions on spine microarchitecture are unknown. In the DATA and DATA-Switch studies, 94 postmenopausal osteoporotic women were randomized to receive 24 mo of teriparatide (20 µg daily), denosumab (60 mg every 6 mo), or both. Then, women originally assigned to 24 mo of teriparatide received 24 mo of denosumab, whereas subjects originally randomized to 24 mo of denosumab received 24 mo of teriparatide. Subjects who received both drugs received an additional 24 mo of denosumab alone. Spine trabecular bone score (TBS, a gray-level textural assessment of bone microarchitecture) was measured blinded from treatment groups using images from 2-dimensional dual-energy X-ray absorptiometry spine scans at 0, 12, 24, 30, 36, and 48 mo in 65 women who had posterior-anterior spine dual-energy X-ray absorptiometry images suitable for TBS analysis. After 24 mo, TBS increased by 2.7 ± 4.7% in the teriparatide group (p = 0.009 vs baseline), by 1.8 ± 5.0% in the denosumab group (p = 0.118 vs baseline), and by 4.5 ± 6.7% in the combination group (p = 0.017 vs baseline), with no significant between-group differences. In the 6 mo after the treatments were switched (months 24-30), TBS continued to increase in the combination-to-denosumab and teriparatide-to-denosumab groups but decreased by -1.1 ± 4.0% in the denosumab-to-teriparatide group (p < 0.05 vs other groups). After 48 mo, compared to month 0, TBS increased by 5.1 ± 5.8% in the teriparatide-to-denosumab group, by 3.6 ± 4.2% in the denosumab-to-teriparatide group, and by 6.1 ± 4.7% in the combination-to-denosumab group (p < 0.001 vs baseline for all groups, p = not significant for between-group differences). Switching from teriparatide to denosumab also increased spine TBS. Conversely, switching from denosumab to teriparatide transiently degraded spine trabecular microarchitecture, the clinical consequences of which require further study.
在绝经后女性中,联合使用特立帕肽和地诺单抗2年比单独使用任何一种药物都能更大程度地增加骨矿物质密度,并且从联合用药或特立帕肽转换为地诺单抗再额外治疗2年可进一步增加骨矿物质密度。相反,从地诺单抗转换为特立帕肽会导致短暂的骨质流失。这些干预措施对脊柱微结构的影响尚不清楚。在DATA和DATA-Switch研究中,94名绝经后骨质疏松女性被随机分配接受24个月的特立帕肽(每日20μg)、地诺单抗(每6个月60mg)或两者联合治疗。然后,最初分配接受24个月特立帕肽治疗的女性接受24个月的地诺单抗治疗,而最初随机接受24个月地诺单抗治疗的受试者接受24个月的特立帕肽治疗。接受两种药物治疗的受试者单独接受额外24个月的地诺单抗治疗。使用来自二维双能X线吸收法脊柱扫描的图像,在65名具有适合TBS分析的前后位脊柱双能X线吸收法图像的女性中,在0、12、24、30、36和48个月时对脊柱小梁骨评分(TBS,一种对骨微结构的灰度纹理评估)进行盲法测量。24个月后,特立帕肽组的TBS增加了2.7±4.7%(与基线相比p=0.009),地诺单抗组增加了1.8±5.0%(与基线相比p=0.118),联合治疗组增加了4.5±6.7%(与基线相比p=0.017),组间差异无统计学意义。在治疗转换后的6个月(24至30个月),联合治疗转地诺单抗组和特立帕肽转地诺单抗组的TBS继续增加,但地诺单抗转特立帕肽组的TBS下降了-1.1±4.0%(与其他组相比p<0.05)。48个月后,与0个月相比,特立帕肽转地诺单抗组的TBS增加了5.1±5.8%,地诺单抗转特立帕肽组增加了3.6±4.2%,联合治疗转地诺单抗组增加了6.1±4.7%(所有组与基线相比p<0.001,组间差异无统计学意义)。从特立帕肽转换为地诺单抗也增加了脊柱TBS。相反,从地诺单抗转换为特立帕肽会使脊柱小梁微结构暂时退化,其临床后果需要进一步研究。