Zinc and vitamin D deficiency and supplementation in hypophosphatasia patients

TY - JOUR

T1 - Zinc and vitamin D deficiency and supplementation in hypophosphatasia patients

T2 - A retrospective study

AU - Wiedemann, Philip

AU - Schmidt, Felix N

AU - Amling, Michael

AU - Yorgan, Timur A

AU - Barvencik, Florian

N1 - Copyright © 2023. Published by Elsevier Inc.

PY - 2023/10

Y1 - 2023/10

N2 - Hypophosphatasia (HPP) is characterized by severe skeletal symptoms including mineralization defects, insufficiency fractures, and delayed facture healing or non-unions. HPP is caused by mutations of the tissue non-specific alkaline phosphatase (TNSALP). Zinc is a cofactor of TNSALP and vitamin D an important regulator of bone matrix mineralization. Data from this retrospective study indicates that deficiencies in zinc or vitamin D occur in HPP patients with a similar frequency as in the general population. While guidelines for repletion of these micronutrients have been established for the general population, the transferability of the efficacy and safety of these regiments to HPP patients still needed to be determined. We filtered for variant classification (ACMG 3-5, non-benign) and data completeness from a total cohort of 263 HPP patients. 73.5 % of this sub-cohort were vitamin D deficient while 27.2 % were zinc deficient. We retrospectively evaluated the effect of supplementation according to general guidelines in 10 patients with zinc-deficiency and 38 patients with vitamin d-deficiency. The treatments significantly raised serum zinc or vitamin D levels respectively. All other assessed disease markers (alkaline phosphatase, pyrodoxal-5-phosphate) or bone turnover markers (phosphate, calcium, parathyroid hormone, bone specific alkaline phosphatase, creatinine, desoxypyridinoline) remained unchanged. These results highlight that general guidelines for zinc and vitamin D repletion can be successfully applied to HPP patients in order to prevent deficiency symptoms without exacerbating the disease burden or causing adverse effects due to changes in bone and calcium homeostasis.

AB - Hypophosphatasia (HPP) is characterized by severe skeletal symptoms including mineralization defects, insufficiency fractures, and delayed facture healing or non-unions. HPP is caused by mutations of the tissue non-specific alkaline phosphatase (TNSALP). Zinc is a cofactor of TNSALP and vitamin D an important regulator of bone matrix mineralization. Data from this retrospective study indicates that deficiencies in zinc or vitamin D occur in HPP patients with a similar frequency as in the general population. While guidelines for repletion of these micronutrients have been established for the general population, the transferability of the efficacy and safety of these regiments to HPP patients still needed to be determined. We filtered for variant classification (ACMG 3-5, non-benign) and data completeness from a total cohort of 263 HPP patients. 73.5 % of this sub-cohort were vitamin D deficient while 27.2 % were zinc deficient. We retrospectively evaluated the effect of supplementation according to general guidelines in 10 patients with zinc-deficiency and 38 patients with vitamin d-deficiency. The treatments significantly raised serum zinc or vitamin D levels respectively. All other assessed disease markers (alkaline phosphatase, pyrodoxal-5-phosphate) or bone turnover markers (phosphate, calcium, parathyroid hormone, bone specific alkaline phosphatase, creatinine, desoxypyridinoline) remained unchanged. These results highlight that general guidelines for zinc and vitamin D repletion can be successfully applied to HPP patients in order to prevent deficiency symptoms without exacerbating the disease burden or causing adverse effects due to changes in bone and calcium homeostasis.

U2 - 10.1016/j.bone.2023.116849

DO - 10.1016/j.bone.2023.116849

M3 - SCORING: Journal article

C2 - 37487860

VL - 175

JO - BONE

JF - BONE

SN - 8756-3282

M1 - 116849

ER -