Clinical, radiographic and biochemical characteristics of adult hypophosphatasia

Schmidt, T.<sup>1,2</sup>; Mussawy, H.<sup>2</sup>; Rolvien, T.<sup>1</sup>; Hawellek, T.<sup>2</sup>; Hubert, J.<sup>2</sup>; Rüther, W.<sup>2</sup>; Amling, M.<sup>1</sup>; Barvencik, F.<sup>1</sup>

Affiliations

¹Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Lottestraße 59, 22529 Hamburg, Germany

²Department of Orthopaedic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany

Abstract and keywords

Summary: In this study, we report on clinical, radiographic and biochemical characteristics of 38 patients with adult hypophosphatasia. High-resolution peripheral quantitative computed tomography showed alterations of bone microstructure in a subgroup of 14 patients. Pyridoxal-5-phosphate levels correlated with the occurrence of fractures and the number of symptoms.

Introduction: Hypophosphatasia (HPP) is a rare disorder with a wide range of clinical manifestations. A reduced enzymatic activity of alkaline phosphatase (ALP) is the key marker of the disease, causing an accumulation of ALP substrates such as pyridoxal-5-phosphate (PLP). The purpose of this retrospective study was to further characterize adult onset HPP.

Methods: We assessed clinical, radiographic and laboratory characteristics of 38 adult patients with HPP. Diagnosis of HPP was established by the combination of low-serum ALP, raised PLP levels and typical symptoms and was genetically confirmed in 32 patients. Dual-energy X-ray absorptiometry (DXA) and laboratory data were available in most patients. High-resolution peripheral quantitative computed tomography (HR-pQCT) was performed in 14 patients.

Results: Clinical characteristics included a wide spectrum of symptoms. A history of fracture was present in 15 patients (39%). Twenty-one patients (55%) complained about recurring headaches, 23 patients (61%) had recurring muscle pain, 4 patients (11%) suffered from severe muscle weakness and 18 patients (47%) showed dental abnormalities. Z-scores assessed by DXA were only slightly reduced in most adult HPP patients. HR-pQCT of 14 patients showed microstructural changes of trabecular and cortical bone compared to reference values of healthy subjects. The occurrence of fractures and multiple symptoms (>2 typical HPP symptoms) were associated with significantly elevated levels of PLP.

Conclusion: Adult HPP presents with a wide range of clinical symptoms and is not associated with low bone mass in general. PLP seems to be a good marker for disease severity in adult patients as its level is correlated with the occurrence of fractures and number of symptoms.

Keywords: Alkaline phosphatase; ALPL; Pyridoxal-5-phosphate; Rare bone diseases

Links

DOI: 10.1007/s00198-017-4087-z

PubMed: 28547134

WoS: 000407492700014

History

Received: 2016-08-27

Accepted: 2017-05-10

Online: 2017-05-25

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Cited By (11)

Year	Entry
2020	Simmons JH, Rush ET, Petryk A, Zhou S, Martos-Moreno GÁ. Dual X-ray absorptiometry has limited utility in detecting bone pathology in children with hypophosphatasia: a pooled post hoc analysis of asfotase alfa clinical trial data. Bone. August 2020;137:115413.
2021	Durrough C, Colazo JM, Simmons J, Hu J-R, Hudson M, Black M, de Riesthal M, Dahir K. Characterization of physical, functional, and cognitive performance in 15 adults with hypophosphatasia. Bone. January 2021;142:115695.
2021	Stürznickel J, Schmidt FN, von Vopelius E, Delsmann MM, Schmidt C, Jandl NM, Oheim R, Barvencik F. Bone healing and reactivation of remodeling under asfotase alfa therapy in adult patients with pediatric-onset hypophosphatasia. Bone. February 2021;143:115794.
2021	Desborough R, Nicklin P, Gossiel F, Balasubramanian M, Walsh JS, Petryk A, Teynor M, Eastell R. Clinical and biochemical characteristics of adults with hypophosphatasia attending a metabolic bone clinic. Bone. March 2021;144:115795.
2022	Hepp N, Folkestad L, Møllebæk S, Frederiksen AL, Duno M, Jørgensen NR, Hermann AP, Jensen J-EB. Bone-microarchitecture and bone-strength in a sample of adults with hypophosphatasia and a matched reference population assessed by HR-pQCT and impact microindentation. Bone. July 2022;160:116420.
2022	Shajani-Yi Z, Ayala-Lopez N, Black M, Dahir KM. Urine phosphoethanolamine is a specific biomarker for hypophosphatasia in adults. Bone. October 2022;163:116504.
2021	Jandl NM, Schmidt T, Rolvien T, Stürznickel J, Chrysostomou K, von Vopelius E, Volk AE, Schinke T, Kubisch C, Amling M, Barvencik F. Genotype–phenotype associations in 72 adults with suspected ALPL-associated hypophosphatasia. Calcif Tiss Int. March 2021;108(3):288-301.
2020	Seefried L, Dahir K, Petryk A, Högler W, Linglart A, Martos‐Moreno GÁ, Ozono K, Fang S, Rockman‐Greenberg C, Kishnani PS. Burden of illness in adults with hypophosphatasia: data from the global hypophosphatasia patient registry. J Bone Miner Res. November 2020;35(11):2171-2178.
2020	Bianchi ML, Bishop NJ, Guañabens N, Hofmann C, Jakob F, Roux C, Zillikens MC; Rare Bone Disease Action Group of the European Calcified Tissue Society. Hypophosphatasia in adolescents and adults: overview of diagnosis and treatment. Osteoporos Int. August 2020;31(8):1445-1460.
2020	Martins L, dos Santos EL, de Almeida AB, Machado RA, Lyrio AM, Foster BL, Kantovitz KR, Coletta RD, Nociti FH Jr. A novel de novo heterozygous ALPL nonsense mutation associated with adult hypophosphatasia. Osteoporos Int. November 2020;31(11):2251-2257.
2021	Genest F, Claußen L, Rak D, Seefried L. Bone mineral density and fracture risk in adult patients with hypophosphatasia. Osteoporos Int. February 2021;32(2):377-385.