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Osteologie 2024; 33(03): 175-184
DOI: 10.1055/a-2360-4737
Review

Supplements in Rare Bone Diseases

Nahrungsergänzungsmittel bei seltenen Knochenerkrankungen
Benjamin Hadzimuratovic 
1   1. Medizinische Abteilung, Hanusch-Krankenhaus, Wien, Austria
,
Lisa Lechner
2   1st Medical Department Hanusch Hospital, Ludwig Boltzmann-Institute of Osteology, Vienna, Austria
3   Diploma Programme MedUni Vienna, Medical University of Vienna, Vienna, Austria
,
Heinrich Resch
4   Fakultät für Medizin, Sigmund Freud Private University Vienna, Wien, Austria
5   II. Medizinische Abteilung, Krankenhaus der Barmherzigen Schwestern Wien, Wien, Austria
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Abstract

Despite having different aetiologies, different rare bone diseases (RBDs) such as hypophosphatasia (HPP), autosomal dominant hypophosphatemic rickets (ADHR), X-linked hypophosphatemia (XLH) and osteogenesis imperfecta (OI) share common clinical features such as growth disturbances, pathological fractures, pseudo-fractures and chronic musculoskeletal pain. The role of micronutrients including minerals, trace elements and vitamin D in the physiological bone metabolism are well established. A significant share of RBD patients suffer from nutritional deficiencies due to the underlying disease or do not achieve the recommended daily intake (RDI) for micronutrients. The supplementation of micronutrients in RBDs should have the goal of achieving the RDI and promoting bone metabolism without increasing the burden of disease. Specific diets and an increased intake of specific micronutrients could potentially improve some of the disease symptoms, however special caution should be taken to avoid over-supplementation and to avoid adverse effects such as hypercalciuria, ectopic calcifications, GI-upset and nephrocalcinosis in case of calcium over-supplementation.

Zusammenfassung

Trotz unterschiedlicher Ätiologien weisen verschiedene seltene Knochenerkrankungen (RBDs) wie Hypophosphatasie (HPP), autosomal-dominante hypophosphatämische Rachitis (ADHR), X-chromosomale Hypophosphatämie (XLH) und Osteogenesis imperfecta (OI) gemeinsame klinische Merkmale auf, die Wachstumsverzögerung, pathologische Frakturen, Pseudofrakturen und chronische muskuloskelettale Schmerzen beinhalten. Die Rolle von Mikronährstoffen wie Mineralien, Spurenelementen und Vitamin D im physiologischen Knochenstoffwechsel ist gut belegt. Ein erheblicher Anteil der RBD-Patienten leidet unter Nährstoffdefiziten durch ihre Grunderkrankung oder erreicht nicht die empfohlene Tagesdosis (RDI) an Mikronährstoffen. Die Supplementation von Mikronährstoffen in RBDs sollte darauf abzielen, die RDI zu erreichen und den Knochenstoffwechsel zu fördern, ohne die Krankheitslast zu erhöhen. Spezifische Diätformen und eine erhöhte Aufnahme einzelner Mikronährstoffe könnten möglicherweise einzelne Krankheitssymptome verbessern. Es ist jedoch besondere Vorsicht geboten, um eine übermäßige Supplementierung und Nebenwirkungen wie Hyperkalzurie, ektopische Verkalkungen, Magen-Darm-Beschwerden und Nephrokalzinose, als Beispiel zu hoher Kalzium-Zufuhr, zu vermeiden.

Keywords

supplements - rare bone diseases - xlh - osteogenesis imperfecta - hypophosphatasia

Schlüsselwörter

Nahrungsergänzungsmittel - seltene Knochenerkrankungen - xlh - Hypophosphatasie - Osteogenesis Imperfecta


Publication History

Received: 13 March 2024

Accepted: 03 July 2024

Article published online:
19 August 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Sabir AH, Cole T. The evolving therapeutic landscape of genetic skeletal disorders. Orphanet J Rare Dis 2019; 14: 1-20
    CrossrefPubMedSearch in Google Scholar
  • 2 Tosi LL, Warman ML. Mechanistic and therapeutic insights gained from studying rare skeletal diseases. Bone 2015; 76: 67-75
    CrossrefPubMedSearch in Google Scholar
  • 3 Unger S, Ferreira CR, Mortier GR. et al. Nosology of genetic skeletal disorders: 2023 revision. Am J Med Genet Part A 2023; 191: 1164-1209
    CrossrefPubMedSearch in Google Scholar
  • 4 Seefried L, Dahir K, Petryk A. et al. Burden of Illness in Adults With Hypophosphatasia: Data From the Global Hypophosphatasia Patient Registry. J Bone Miner Res 2020; 35: 2171-2178
    CrossrefPubMedSearch in Google Scholar
  • 5 Skalny AV, Aschner M, Silina EV. et al. The Role of Trace Elements and Minerals in Osteoporosis: A Review of Epidemiological and Laboratory Findings. Biomolecules 2023; 13: 1-33
    CrossrefPubMedSearch in Google Scholar
  • 6 Prié D, Friedlander G. Genetic Disorders of Renal Phosphate Transport. N Engl J Med 2010; 362: 2399-2409
    CrossrefPubMedSearch in Google Scholar
  • 7 Wiedemann P, Schmidt FN, Amling M. et al. Zinc and vitamin D deficiency and supplementation in hypophosphatasia patients – A retrospective study. Bone 2023; 175: 116849
    CrossrefPubMedSearch in Google Scholar
  • 8 Farman MR, Rehder C, Malli T. et al. The Global ALPL gene variant classification project: Dedicated to deciphering variants. Bone 2024; 178
    CrossrefPubMedSearch in Google Scholar
  • 9 Millán JL, Whyte MP. Alkaline Phosphatase and Hypophosphatasia. Calcif Tissue Int 2016; 98: 398-416
    CrossrefPubMedSearch in Google Scholar
  • 10 Shajani-Yi Z, Ayala-Lopez N, Black M. et al. Urine phosphoethanolamine is a specific biomarker for hypophosphatasia in adults. Bone 2022; 163: 116504
    CrossrefPubMedSearch in Google Scholar
  • 11 Shapiro JR, Lewiecki EM. Hypophosphatasia in Adults: Clinical Assessment and Treatment Considerations. J Bone Miner Res 2017; 32: 1977-1980
    CrossrefPubMedSearch in Google Scholar
  • 12 Seefried L. Treatment of hypophosphatasia. Int J Bone Fragility 2023; 3: 16-21
    CrossrefSearch in Google Scholar
  • 13 Fonta C, Salles JP. Neuromuscular features of hypophosphatasia. Arch Pediatr 2017; 24: 5S85-5S88
    CrossrefPubMedSearch in Google Scholar
  • 14 Gennero I, Conte-Auriol F, Salles JP. Laboratory diagnosis of hypophosphatasia. Arch Pediatr 2017; 24: 5S57-5S60
    CrossrefPubMedSearch in Google Scholar
  • 15 Society GN. New reference values for Vitamin DGermany. Ann Nutr Metab 2012; 60: 241-246
    CrossrefPubMedSearch in Google Scholar
  • 16 Whyte MP, Greenberg CR, Salman NJ. et al. Enzyme-Replacement Therapy in Life-Threatening Hypophosphatasia. 2012 366. 904–913
    PubMedSearch in Google Scholar
  • 17 Sönmez AB, Arifoğlu İ, Yıldırım A. et al. Benign transient hyperphosphatasemia in an infant during zinc supplementation. Turk Pediatr Ars 2018; 53: 120-123
    CrossrefPubMedSearch in Google Scholar
  • 18 Sakata KI, Hashimoto A, Kambe T. et al. Expression analysis of zinc-metabolizing enzymes in the saliva as a new method of evaluating zinc content in the body: two case reports and a review of the literature. J Med Case Rep 2024; 18: 1-7
    CrossrefPubMedSearch in Google Scholar
  • 19 Haase H, Ellinger S, Linseisen J. et al. Revised D-A-CH-reference values for the intake of zinc. J Trace Elem Med Biol 2020; 61: 126536
    CrossrefPubMedSearch in Google Scholar
  • 20 Kuehn K, Hahn A, Seefried L. Mineral Intake and Clinical Symptoms in Adult Patients with Hypophosphatasia. J Clin Endocrinol Metab 2020; 105: E2982-E2992
    CrossrefPubMedSearch in Google Scholar
  • 21 Kuehn K, Hahn A, Seefried L. Impact of Restricted Phosphorus, Calcium-adjusted Diet on Musculoskeletal and Mental Health in Hypophosphatasia. J Endocr Soc 2023; 8: 1-11
    CrossrefPubMedSearch in Google Scholar
  • 22 DGE, ÖGE. Referenzwerte für die Nährstoffzufuhr. 2. Aufl. 2024
  • 23 Whyte MP, Zhang F, Wenkert D. et al. Hypophosphatasia: Vitamin B6 status of affected children and adults. Bone 2022; 154
    CrossrefPubMedSearch in Google Scholar
  • 24 Vrolijk MF, Opperhuizen A, Jansen EHJM. et al. The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function. Toxicol Vitr 2017; 44: 206-212
    CrossrefPubMedSearch in Google Scholar
  • 25 Beck-Nielsen SS, Mughal Z, Haffner D. et al. FGF23 and its role in X-linked hypophosphatemia-related morbidity. Orphanet J Rare Dis 2019; 14: 1-25
    CrossrefPubMedSearch in Google Scholar
  • 26 Shimada T, Mizutani S, Muto T. et al. Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. Proc Natl Acad Sci U S A 2001; 98: 6500-6505
    CrossrefPubMedSearch in Google Scholar
  • 27 Haffner D, Emma F, Eastwood DM. et al. Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia. Nat Rev Nephrol 2019; 15: 435-455
    CrossrefPubMedSearch in Google Scholar
  • 28 Mindler GT, Kranzl A, Stauffer A. et al. Lower Limb Deformity and Gait Deviations Among Adolescents and Adults With X-Linked Hypophosphatemia. Front Endocrinol (Lausanne) 2021; 12: 1-10
    CrossrefPubMedSearch in Google Scholar
  • 29 Ariceta G, Beck-Nielsen SS, Boot AM. et al. The International X-Linked Hypophosphatemia (XLH) Registry: first interim analysis of baseline demographic, genetic and clinical data. Orphanet J Rare Dis 2023; 18: 1-17
    CrossrefPubMedSearch in Google Scholar
  • 30 Lambert A, Zhukouskaya V, Rothenbuhler A. et al. X-linked hypophosphatemia: Management and treatment prospects To cite this version: HAL Id: hal-03489008. 2021
  • 31 Carpenter TO, Whyte MP, Imel EA. et al. Burosumab Therapy in Children with X-Linked Hypophosphatemia. N Engl J Med 2018; 378: 1987-1998
    CrossrefPubMedSearch in Google Scholar
  • 32 Fratzl-Zelman N, Gamsjaeger S, Blouin S. et al. Alterations of bone material properties in adult patients with X-linked hypophosphatemia (XLH). J Struct Biol 2020; 211: 107556
    CrossrefPubMedSearch in Google Scholar
  • 33 De Paula Colares Neto G, Yamauchi FI, Baroni RH. et al. Nephrocalcinosis and nephrolithiasis in X-linked hypophosphatemic rickets: Diagnostic imaging and risk factors. J Endocr Soc 2019; 3: 1053-1061
    CrossrefPubMedSearch in Google Scholar
  • 34 Farrow EG, Yu X, Summers LJ. et al. Iron deficiency drives an autosomal dominant hypophosphatemic rickets (ADHR) phenotype in fibroblast growth factor-23 (Fgf23) knock-in mice. Proc Natl Acad Sci U S A 2011; 108
    CrossrefPubMedSearch in Google Scholar
  • 35 Imel EA, Peacock M, Gray AK. et al. Iron modifies plasma FGF23 differently in autosomal dominant hypophosphatemic rickets and healthy humans. J Clin Endocrinol Metab 2011; 96: 3541-3549
    CrossrefPubMedSearch in Google Scholar
  • 36 Wolf M, Rubin J, Achebe M. et al. Effects of Iron Isomaltoside vs Ferric Carboxymaltose on Hypophosphatemia in Iron-Deficiency Anemia: Two Randomized Clinical Trials. JAMA – J Am Med Assoc 2020; 323: 432-443
    CrossrefPubMedSearch in Google Scholar
  • 37 Dwan K, Phillipi CA, Steiner RD. et al. Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database Syst Rev 2016; 2016
    CrossrefSearch in Google Scholar
  • 38 Castillo H, Samson-Fang L. Effects of bisphosphonates in children with osteogenesis imperfecta: An AACPDM systematic review. Dev Med Child Neurol 2009; 51: 17-29
    CrossrefPubMedSearch in Google Scholar
  • 39 Germain-Lee EL, Brennen FS, Stern D. et al. Cross-sectional and longitudinal growth patterns in osteogenesis imperfecta: Implications for clinical care. Pediatr Res 2016; 79: 489-495
    CrossrefPubMedSearch in Google Scholar
  • 40 Zambrano MB, Brizola ES, Refosco L. et al. Anthropometry, Nutritional Status, and Dietary Intake in Pediatric Patients with Osteogenesis Imperfecta. J Am Coll Nutr 2014; 33: 18-25
    CrossrefPubMedSearch in Google Scholar
  • 41 Zambrano MB, Félix TM, Mello ED. Calcium intake improvement after nutritional intervention in paediatric patients with osteogenesis imperfecta. J Hum Nutr Diet 2019; 32: 619-624
    CrossrefPubMedSearch in Google Scholar
  • 42 Strohm D. New reference values for calcium. Ann Nutr Metab 2013; 63: 186-192
    CrossrefPubMedSearch in Google Scholar
  • 43 Hamza RT, Abdelaziz TH, Elakkad M. Anthropometric and parameters in egyptian children and adolescents with osteogenesis imperfecta. Horm Res Paediatr 2015; 83: 311-320
    CrossrefPubMedSearch in Google Scholar
  • 44 Plante L, Veilleux LN, Glorieux FH. et al. Effect of high-dose vitamin D supplementation on bone density in youth with osteogenesis imperfecta: A randomized controlled trial. Bone 2016; 86: 36-42
    CrossrefPubMedSearch in Google Scholar
  • 45 Zambrano MB, Brizola E, Pinheiro B. et al. Study of the Determinants of Vitamin D Status in Pediatric Patients With Osteogenesis Imperfecta. J Am Coll Nutr 2016; 35: 339-345
    CrossrefPubMedSearch in Google Scholar
  • 46 Salles JP. Hypophosphatasia: Biological and Clinical Aspects, Avenues for Therapy. Clin Biochem Rev 2020; 41: 13-27
    CrossrefPubMedSearch in Google Scholar
  • 47 Makris K, Mousa C, Cavalier E. Alkaline Phosphatases: Biochemistry, Functions, and Measurement. Calcif Tissue Int 2023; 233-242
    CrossrefPubMedSearch in Google Scholar
  • 48 Stiles LI, Ferrao K, Mehta KJ. Role of zinc in health and disease. Clin Exp Med 2024; 24
    CrossrefPubMedSearch in Google Scholar
  • 49 Carpenter TO, Imel EA, Holm IA. et al. A clinician’s guide to X-linked hypophosphatemia. J Bone Miner Res 2011; 26: 1381-1388
    CrossrefPubMedSearch in Google Scholar