Recovery of bone mineralization and quality during asfotase alfa treatment in an adult patient with infantile-onset hypophosphatasia

Tim Rolvien; Tobias Schmidt; Felix N Schmidt; Simon von Kroge; Björn Busse; Michael Amling; Florian Barvencik

doi:10.1016/j.bone.2019.05.036

Recovery of bone mineralization and quality during asfotase alfa treatment in an adult patient with infantile-onset hypophosphatasia

Standard

Recovery of bone mineralization and quality during asfotase alfa treatment in an adult patient with infantile-onset hypophosphatasia. / Rolvien, Tim; Schmidt, Tobias; Schmidt, Felix N ; von Kroge, Simon ; Busse, Björn ; Amling, Michael ; Barvencik, Florian.

In: BONE, Vol. 127, 10.2019, p. 67-74.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Rolvien, T, Schmidt, T, Schmidt, FN , von Kroge, S , Busse, B , Amling, M & Barvencik, F 2019, 'Recovery of bone mineralization and quality during asfotase alfa treatment in an adult patient with infantile-onset hypophosphatasia', BONE, vol. 127, pp. 67-74. https://doi.org/10.1016/j.bone.2019.05.036

APA

Rolvien, T., Schmidt, T., Schmidt, F. N., von Kroge, S., Busse, B., Amling, M., & Barvencik, F. (2019). Recovery of bone mineralization and quality during asfotase alfa treatment in an adult patient with infantile-onset hypophosphatasia. BONE, 127, 67-74. https://doi.org/10.1016/j.bone.2019.05.036

Vancouver

Rolvien T, Schmidt T, Schmidt FN , von Kroge S , Busse B , Amling M et al. Recovery of bone mineralization and quality during asfotase alfa treatment in an adult patient with infantile-onset hypophosphatasia. BONE. 2019 Oct;127:67-74. https://doi.org/10.1016/j.bone.2019.05.036

Bibtex

@article{0e66901448a04546b5a1fa7ecd3b4eed,

title = "Recovery of bone mineralization and quality during asfotase alfa treatment in an adult patient with infantile-onset hypophosphatasia",

abstract = "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.",

keywords = "Journal Article",

author = "Tim Rolvien and Tobias Schmidt and Schmidt, {Felix N} and {von Kroge}, Simon and Bj{\"o}rn Busse and Michael Amling and Florian Barvencik",

note = "Copyright {\textcopyright} 2019. Published by Elsevier Inc.",

year = "2019",

month = oct,

doi = "10.1016/j.bone.2019.05.036",

language = "English",

volume = "127",

pages = "67--74",

journal = "BONE",

issn = "8756-3282",

publisher = "Elsevier Inc.",

}

RIS

TY - JOUR

T1 - Recovery of bone mineralization and quality during asfotase alfa treatment in an adult patient with infantile-onset hypophosphatasia

AU - Rolvien, Tim

AU - Schmidt, Tobias

AU - Schmidt, Felix N

AU - von Kroge, Simon

AU - Busse, Björn

AU - Amling, Michael

AU - Barvencik, Florian

PY - 2019/10

Y1 - 2019/10

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1016/j.bone.2019.05.036

DO - 10.1016/j.bone.2019.05.036

M3 - SCORING: Journal article

C2 - 31152801

VL - 127

SP - 67

EP - 74

JO - BONE

JF - BONE

SN - 8756-3282

ER -