Roberts J, Castro C, Moore A E B, Fogelman I, Hampson G
Department of Chemical Pathology and Metabolic Medicine, St Thomas' Hospital, London, UK.
Metabolic Bone Clinic, Department of Rheumatology, Guy's Hospital, London, UK.
Clin Endocrinol (Oxf). 2016 Apr;84(4):509-15. doi: 10.1111/cen.13012. Epub 2016 Feb 8.
Treatment discontinuation after long-term bisphosphonate (BP), termed a 'drug holiday', has been proposed to reduce the risk of BP-associated complications. The duration of treatment cessation remains unclear. Changes in bone mineral density (BMD), bone turnover markers (BTMs) and their relationship with FRAX were assessed to help determine the optimum length of a 'drug holiday'.
A retrospective analysis of 134 patients (13M, 121F) aged [mean (SD)] 68·4 (8·2) years who discontinued BPs after treatment for 5·9 (3·0) years for osteoporosis was undertaken. BMD at the lumbar spine (LS), total hip (TH), and femoral neck (FN) and biochemical parameters including serum 25 (OH) vitamin D, bone turnover markers (plasma CTX, P1NP) and FRAX scores were determined at discontinuation, 12-18 months and 24-30 months off treatment.
BMD decreased significantly at the LS [% change mean (SD): -0·94 (3·6), P = 0·008], TH [-1·4 (2·4), P < 0·001] and FN [-1·8 (4·4), P < 0·001] after treatment discontinuation for 12-18 months. In the subgroup who remained off treatment for 24-30 months, a progressive decline in BMD was seen at the TH and FN with total % decrease of -2·52 (3·5) and -2·7 (4·76), P < 0·001, respectively. CTX and P1NP increased significantly at 12-18 months after discontinuation [% change CTX: 95 (88), P < 0·001, P1NP: 88 (73), P < 0·001]. FRAX scores were significant predictors of % change in BMD at the FN (P < 0·05), independently of bone turnover and vitamin D status. In summary, our data show that following a 'drug holiday', the use of DEXA scans, BTMs and FRAX may help guide when to resume treatment.
长期使用双膦酸盐（BP）后停药，即所谓的“药物假期”，已被提议用于降低与BP相关并发症的风险。治疗停药的持续时间尚不清楚。评估骨矿物质密度（BMD）、骨转换标志物（BTMs）的变化及其与FRAX的关系，以帮助确定“药物假期”的最佳时长。
对134例患者（13例男性，121例女性）进行回顾性分析，这些患者因骨质疏松接受了5.9（3.0）年的BP治疗后停药，年龄[平均（标准差）]为68.4（8.2）岁。在停药时、停药12 - 18个月和停药24 - 30个月时，测定腰椎（LS）、全髋（TH）和股骨颈（FN）的骨密度以及生化参数，包括血清25（OH）维生素D、骨转换标志物（血浆CTX、P1NP）和FRAX评分。
停药12 - 18个月后，腰椎（平均变化百分比[标准差]：-0.94（3.6），P = 0.008）、全髋（-1.4（2.4），P < 0.001）和股骨颈（-1.8（4.4），P < 0.001）的骨密度显著下降。在停药24 - 30个月的亚组中，全髋和股骨颈的骨密度呈渐进性下降，总下降百分比分别为-2.52（3.5）和-2.7（4.76），P < 0.001。停药后12 - 18个月时，CTX和P1NP显著升高（CTX变化百分比：95（88），P < 0.001，P1NP：88（73），P < 0.001）。FRAX评分是股骨颈骨密度变化百分比的显著预测指标（P < 0.05），独立于骨转换和维生素D状态。总之，我们的数据表明，在“药物假期”之后，使用双能X线吸收法扫描、BTMs和FRAX可能有助于指导何时恢复治疗。
