Bone healing and reactivation of remodeling under asfotase alfa therapy in adult patients with pediatric-onset hypophosphatasia

Stürznickel, Julian; Schmidt, Felix N.; Vopelius, Emil von; Delsmann, Maximilian M.; Schmidt, Constantin; Jandl, Nico Maximilian; Oheim, Ralf; Barvencik, Florian

doi:10.1016/j.bone.2020.115794

Cited by 17 publications

(16 citation statements)

References 38 publications

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“…Bone is subjected to different doses of irradiation, ranging from mGy to kGy, in both clinical [ [28] , [29] , [30] ] and research applications [ 2 , 3 , 8 , 9 , 31 ]. Although the risk of radiation to the human body is well documented, the benefits of techniques requiring radiation in clinical imaging outweigh the potential risks.…”

Section: Discussionmentioning

confidence: 99%

Influence of X-rays and gamma-rays on the mechanical performance of human bone factoring out intraindividual bone structure and composition indices

Schmidt

Hahn

Stockhausen

et al. 2022

Materials Today Bio

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Doses of irradiation above 25 kGy are known to cause irreversible mechanical decay in bone tissue. However, the impact of irradiation doses absorbed in a clinical setting on the mechanical properties of bone remains unclear. In daily clinical practice and research, patients and specimens are exposed to irradiation due to diagnostic imaging tools, with doses ranging from milligray to Gray. The aim of this study was to investigate the influence of irradiation at these doses ranges on the mechanical performance of bone independent of inter-individual bone quality indices. Therefore, cortical bone specimens (n = 10 per group) from a selected organ donor were irradiated at doses of milligray, Gray and kilogray (graft tissue sterilization) at five different irradiation doses. Three-point bending was performed to assess mechanical properties in the study groups. Our results show a severe reduction in mechanical performance (work to fracture: 50.29 ± 11.49 Nmm in control, 14.73 ± 1.84 Nmm at 31.2 kGy p ≤ 0.05) at high irradiation doses of 31.2 kGy, which correspond to graft tissue sterilization or synchrotron imaging. In contrast, no reduction in mechanical properties were detected for doses below 30 Gy. These findings are further supported by fracture surface texture imaging (i.e. more brittle fracture textures above 31.2 kGy). Our findings show that high radiation doses (≥31.2 kGy) severely alter the mechanical properties of bone. Thus, irradiation of this order of magnitude should be taken into account when mechanical analyses are planned after irradiation. However, doses of 30 Gy and below, which are common for clinical and experimental imaging (e.g., radiation therapy, DVT imaging, CT imaging, HR-pQCT imaging, DXA measurements, etc.), do not alter the mechanical bending-behavior of bone.

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Section: Discussionmentioning

confidence: 99%

Influence of X-rays and gamma-rays on the mechanical performance of human bone factoring out intraindividual bone structure and composition indices

Schmidt

Hahn

Stockhausen

et al. 2022

Materials Today Bio

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“…In the case of HPP, treatment before 2015 consisted in an attempt to mitigate symptoms by controlling calcium and phosphorus levels. Enzyme replacement therapy with asfotase alfa has gained popularity in recent years [42], although the treatment is not always effective.…”

Section: Gene Therapy In Periodontal Diseasementioning

confidence: 99%

Gene and Cell Therapy in Dental Tissue Regeneration

Pablo¹,

Serrano²,

García-Arranz³

et al. 2022

Human Tooth and Developmental Dental Defects - Compositional and Genetic Implications

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Advanced therapies hold substantial promise for the treatment of periodontal conditions. Gene therapy has the potential to transfer “therapeutic” genes, which express proteins such as bone morphogenetic proteins, osteoprotegerin, and tissue nonspecific alkaline phosphatase, which is deficient in patients with hypophosphatasia, a condition that affects mineralization of teeth and bone. Transferred genes may also express platelet-derived growth factor, which modulates the growth of periodontal tissue and the alveolar bone. As regards cell therapy, several clinical trials have shown that mesenchymal stem cells, when used with different kinds of scaffolds to enable the required three-dimensional environment, possess a bone regeneration potential that is particularly useful in such disorders as osteoporosis and osteonecrosis, or for regenerating alveolar bone (osseointegration) prior to placing a dental implant. However, much work is still required before these new therapies become true alternatives in routine clinical dental practice. Medical advances require investments, which are usually influenced by the priorities of both politicians and society at large. This will contribute to promoting innovation, efficient treatments, medium- and long-term savings, and a higher quality of life.

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“…Recent studies have shown the effectiveness of asfotase alfa treatment in adults and adolescents with pediatric-onset HPP, showing an improvement of osseous consolidation of non-unions [ 119 ], a normalization of circulating TNSALP substrate levels, and improved functional abilities and health-related quality of life [ 119 , 120 , 121 ], without severe adverse events.…”

Section: Treatment Of Hppmentioning

confidence: 99%

Hypophosphatasia: A Unique Disorder of Bone Mineralization

Villa-Suárez

García-Fontana

Andújar-Vera

et al. 2021

IJMS

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Hypophosphatasia (HPP) is a rare genetic disease characterized by a decrease in the activity of tissue non-specific alkaline phosphatase (TNSALP). TNSALP is encoded by the ALPL gene, which is abundantly expressed in the skeleton, liver, kidney, and developing teeth. HPP exhibits high clinical variability largely due to the high allelic heterogeneity of the ALPL gene. HPP is characterized by multisystemic complications, although the most common clinical manifestations are those that occur in the skeleton, muscles, and teeth. These complications are mainly due to the accumulation of inorganic pyrophosphate (PPi) and pyridoxal-5′-phosphate (PLP). It has been observed that the prevalence of mild forms of the disease is more than 40 times the prevalence of severe forms. Patients with HPP present at least one mutation in the ALPL gene. However, it is known that there are other causes that lead to decreased alkaline phosphatase (ALP) levels without mutations in the ALPL gene. Although the phenotype can be correlated with the genotype in HPP, the prediction of the phenotype from the genotype cannot be made with complete certainty. The availability of a specific enzyme replacement therapy for HPP undoubtedly represents an advance in therapeutic strategy, especially in severe forms of the disease in pediatric patients.

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Bone healing and reactivation of remodeling under asfotase alfa therapy in adult patients with pediatric-onset hypophosphatasia

Cited by 17 publications

References 38 publications

Influence of X-rays and gamma-rays on the mechanical performance of human bone factoring out intraindividual bone structure and composition indices

Influence of X-rays and gamma-rays on the mechanical performance of human bone factoring out intraindividual bone structure and composition indices

Gene and Cell Therapy in Dental Tissue Regeneration

Hypophosphatasia: A Unique Disorder of Bone Mineralization

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