Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria.
J Bone Miner Res. 2014 Feb;29(2):440-9. doi: 10.1002/jbmr.2035.
The spectrum of therapeutic options and the amount of clinical trials for male osteoporosis (mOP) is lower than those for postmenopausal osteoporosis. Therefore, we examined the effects of 24 months of ibandronate (IBN) treatment (3 mg/3 mL intravenously every 3 months) on bone material quality in 19 subjects with mOP within an open-label, single-center, prospective phase III study (Eudract number 2006-006692-20). Patients (median age [25th, 75th percentiles] 53.0 [44.5; 57.0] years) were included if they had low bone mineral density (BMD) and/or at least one low trauma fracture and no secondary cause of osteoporosis. The primary endpoint was to evaluate IBN effects on cancellous (Cn.) and cortical (Ct.) bone mineralization density distribution (BMDD) based on quantitative backscattered electron imaging (qBEI) of paired transiliacal bone biopsies (baseline, 24 months). Secondary endpoints included changes in areal bone mineral density (BMD by dual-energy X-ray absorptiometry [DXA]) and serum markers of bone turnover including type I collagen peptides CrossLaps (CTX), procollagen type 1 amino-terminal propeptide (P1NP), and osteocalcin (OC). At baseline, cancellous bone matrix mineralization from mOP was lower than published reference data (mean degree of mineralization Cn.CaMean -1.8%, p < 0.01). IBN treatment increased calcium concentrations versus baseline (Cn.CaMean +2.4%, Ct.CaMean, +3.0% both p < 0.01), and reduced heterogeneity of mineralization (Cn.CaWidth -14%, p = 0.044; Ct.CaWidth, -16%, p = 0.001), leading to cancellous BMDD within normal range. IBN treatment was associated with a decrease in porosity of mineralized cortical tissue (-25%, p = 0.01); increases in BMD at the lumbar spine, the femoral neck, and the total hip (+3.3%, +1.9%, and +5.6%, respectively, p ≤ 0.01); and reductions in CTX (-37.5%), P1NP (-44.4%), and OC (-36.3%, all p < 0.01). Our BMDD findings are in line with the reduction of bone turnover markers and the increase in BMD by IBN in our patients and suggest that the latter mainly reflects the increase in matrix mineralization and the reduction of cortical porosity in this cohort with mOP.
男性骨质疏松症（mOP）的治疗选择和临床试验数量都低于绝经后骨质疏松症。因此，我们在一项开放标签、单中心、前瞻性 III 期研究（Eudract 编号 2006-006692-20）中，检查了伊班膦酸盐（IBN）治疗 24 个月（每 3 个月静脉注射 3mg/3mL）对 19 例 mOP 患者的骨质量的影响。纳入标准为骨密度低（BMD）和/或至少有一次低创伤性骨折且无骨质疏松症继发原因的患者。主要终点是评估 IBN 对定量背散射电子成像（qBEI）双侧髂骨活检的骨小梁（Cn.）和皮质（Ct.）骨矿化密度分布（BMDD）的影响（基线，24 个月）。次要终点包括通过双能 X 射线吸收法（DXA）测量的面积骨密度（BMD）以及包括 I 型胶原肽 CrossLaps（CTX）、I 型前胶原氨基端前肽（P1NP）和骨钙素（OC）在内的骨转换血清标志物的变化。基线时，mOP 的骨小梁基质矿化程度低于已发表的参考数据（矿化程度均值 Cn.CaMean-1.8%，p<0.01）。IBN 治疗后，钙浓度与基线相比增加（Cn.CaMean+2.4%，Ct.CaMean+3.0%，均 p<0.01），矿化均匀度降低（Cn.CaWidth-14%，p=0.044；Ct.CaWidth-16%，p=0.001），导致骨小梁 BMDD 恢复正常范围。IBN 治疗与矿化皮质组织的孔隙率降低有关（-25%，p=0.01）；腰椎、股骨颈和全髋关节的 BMD 增加（分别为+3.3%、+1.9%和+5.6%，p≤0.01）；CTX（-37.5%）、P1NP（-44.4%）和 OC（-36.3%，均 p<0.01）降低。我们的 BMDD 发现与 IBN 治疗后骨转换标志物的减少和 BMD 的增加相一致，并表明后者主要反映了基质矿化的增加和该队列中 mOP 患者皮质孔隙率的降低。
