Streeten Elizabeth A, Ramirez Sheila, Eliades Myrto, Jaimungal Sarada, Chandrasekaran Sruti, Kathleen Ryan, Holmes Morton D, Puffenberger Erik G, Herskovitz Rita, Leonard Mary B
University of Maryland School of Medicine, Division of Endocrinology, Diabetes & Nutrition, Baltimore, MD, USA.
University of Maryland School of Medicine, Division of Endocrinology, Diabetes & Nutrition, Baltimore, MD, USA.
Bone. 2015 Aug;77:17-23. doi: 10.1016/j.bone.2015.04.007. Epub 2015 Apr 16.
Osteoporosis pseudoglioma syndrome (OPPG) is a rare autosomal recessive disorder of childhood osteoporosis and blindness due to inactivating mutations in LDL receptor-like protein 5 (LRP5). We and others have reported improvement in areal bone mineral density (aBMD) by DXA in OPPG on short term bisphosphonates. Long-term data on bisphosphonate use in OPPG and measures of volumetric BMD (vBMD) and cortical structure are not available. In addition, no long-term DXA data on untreated OPPG is available. The aims of this study were to: (1) record low trauma fractures and longitudinal aBMD by DXA in 5 OPPG patients on chronic bisphosphonate treatment, and in 4 OPPG patients never treated (2) to perform tibia peripheral quantitative CT (pQCT) to evaluate volumetric bone mineral density (vBMD), cortical structure and calf muscle area in 6 OPPG patients and 14 unaffected first degree family members. pQCT results were converted to sex-specific Z-scores for age and adjusted for tibia length based on data in >700 reference participants. We observed 4 fractures (3 femoral shafts) in 3 OPPG patients while on bisphosphonates, after each achieved significant improvement in aBMD. OPPG participants had significantly lower mean trabecular vBMD (-1.51 vs. 0.17, p = 0.002), cortical area (-2.36 vs. 0.37; p < 0.001) and periosteal circumference (-1.86 vs. -0.31, p = 0.001) Z-scores, compared with unaffected participants and had a trend toward lower muscle area Z-score (-0.69 vs. 0.47, p = 0.12). These data demonstrate substantial bone fragility despite improvements in aBMD. The pQCT data provide insight into the fragility with substantial deficits in trabecular vBMD and cortical dimensions, consistent with OPPG effects of bone formation. Treatment that improves bone quality is needed to reduce fractures in OPPG.
骨质疏松假性胶质瘤综合征（OPPG）是一种罕见的常染色体隐性疾病，因低密度脂蛋白受体相关蛋白5（LRP5）的失活突变导致儿童期骨质疏松和失明。我们及其他研究人员曾报道，短期使用双膦酸盐治疗OPPG可使双能X线吸收法（DXA）测量的骨面积密度（aBMD）有所改善。目前尚无关于OPPG长期使用双膦酸盐以及骨体积密度（vBMD）和皮质结构测量的相关数据。此外，也没有未经治疗的OPPG患者的长期DXA数据。本研究的目的是：（1）记录5例接受慢性双膦酸盐治疗的OPPG患者以及4例从未接受治疗的OPPG患者因低创伤导致的骨折情况和通过DXA测量的纵向aBMD；（2）对6例OPPG患者和14例未受影响的一级家庭成员进行胫骨外周定量CT（pQCT）检查，以评估骨体积密度（vBMD）、皮质结构和小腿肌肉面积。根据700多名参考参与者的数据，将pQCT结果转换为按年龄和性别划分的Z值，并根据胫骨长度进行调整。我们观察到3例接受双膦酸盐治疗的OPPG患者发生了4处骨折（3处股骨干骨折），且每例患者的aBMD均有显著改善。与未受影响的参与者相比，OPPG参与者的平均小梁vBMD Z值（-1.51 vs. 0.17，p = 0.002）、皮质面积Z值（-2.36 vs. 0.37；p < 0.001）和骨膜周长Z值（-1.86 vs. -0.31，p = 0.001）显著更低，并且肌肉面积Z值有降低的趋势（-0.69 vs. 0.47，p = 0.12）。这些数据表明，尽管aBMD有所改善，但骨脆性依然严重。pQCT数据揭示了小梁vBMD和皮质尺寸存在显著缺陷的骨脆性情况，这与OPPG对骨形成的影响一致。需要改善骨质的治疗方法来减少OPPG患者的骨折发生。
