Rolvien Tim, Schmidt Tobias, Schmidt Felix N, von Kroge Simon, Busse Björn, Amling Michael, Barvencik Florian
Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Orthopedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Bone. 2019 Oct;127:67-74. doi: 10.1016/j.bone.2019.05.036. Epub 2019 May 30.
Hypophosphatasia (HPP) is a hereditary musculoskeletal disorder characterized by low serum alkaline phosphatase (ALP) activity leading to poor bone mineralization. On a micro-morphological level, this may not only be reflected by an enrichment of osteoid but also a degradation of bone quality. Asfotase alfa is an enzyme replacement therapy that was recently demonstrated to improve bone mineralization as well as clinical status (e.g. growth, muscle strength and quality of life). However, the underlying changes of bone quality parameters on asfotase alfa treatment are currently not known. In the present study, we report a 24-year-old woman with genetically confirmed infantile-onset HPP and recurrent fractures. While the initiated asfotase alfa treatment was followed by rapid clinical improvements (i.e., disappearance of bone marrow edema, increase of muscle strength), the BMD assessed by DXA at the hip and spine increased moderately at two years follow-up. A detailed skeletal assessment using high-resolution peripheral quantitative computed tomography (HR-pQCT) and a high-resolution analysis of two consecutive iliac crest bone biopsies revealed only minor improvements of bone microarchitecture but a remarkable reduction of osteoid parameters. Furthermore, the high mineralization heterogeneity at baseline assessed by quantitative backscattered electron imaging (qBEI) decreased after 2 year of asfotase alfa treatment. Finally, we found an increase in mineral maturation reflected by higher mineral-to-matrix and carbonate-to-phosphate ratios using Fourier transform infrared spectroscopy (FTIR) imaging as well as increased local mechanical properties using reference point indentation (RPI). Taken together, our findings provide evidence for an improvement of bone quality indices beyond the mere reduction of osteoid indices and thereby contribute to the understanding of fracture risk reduction in HPP patients on asfotase alfa treatment.
低磷酸酯酶症（HPP）是一种遗传性肌肉骨骼疾病，其特征是血清碱性磷酸酶（ALP）活性低下，导致骨矿化不良。在微观形态学水平上，这不仅可能表现为类骨质增多，还可能表现为骨质质量下降。阿加糖酶α是一种酶替代疗法，最近已证明其可改善骨矿化以及临床状况（如生长、肌肉力量和生活质量）。然而，目前尚不清楚阿加糖酶α治疗对骨质质量参数的潜在影响。在本研究中，我们报告了一名24岁经基因确诊为婴儿型HPP且反复骨折的女性患者。尽管开始阿加糖酶α治疗后临床迅速改善（即骨髓水肿消失、肌肉力量增强），但在两年随访时，通过双能X线吸收法（DXA）评估的髋部和脊柱骨密度适度增加。使用高分辨率外周定量计算机断层扫描（HR-pQCT）进行详细的骨骼评估以及对连续两次髂嵴骨活检进行高分辨率分析显示，骨微结构仅有轻微改善，但类骨质参数显著降低。此外，通过定量背散射电子成像（qBEI）评估的基线时高矿化异质性在阿加糖酶α治疗2年后降低。最后，我们发现使用傅里叶变换红外光谱（FTIR）成像显示矿物质成熟度增加，表现为矿物质与基质以及碳酸盐与磷酸盐的比率升高，同时使用参考点压痕（RPI）显示局部力学性能增强。综上所述，我们的研究结果为骨质质量指标的改善提供了证据，这种改善不仅仅是类骨质指标的降低，从而有助于理解接受阿加糖酶α治疗的HPP患者骨折风险降低的情况。
