Clinical and radiographic findings in adults with persistent hypophosphatasemia

McKiernan, Fergus Eoin<sup>1</sup>; Berg, Richard L.<sup>2</sup>; Fuehrer, Jay<sup>2</sup>

Affiliations

¹Center for Bone Disease, Marshfield Clinic, Marshfield, WI, USA

²Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, WI, USA

Abstract and keywords

A serum alkaline phosphatase value below the age-adjusted lower limits of normal (hypophosphatasemia) is uncommonly encountered in clinical practice. The electronic and paper medical records of 885,165 patients treated between 2002 and 2012 at a large, rural, multispecialty health clinic were interrogated to estimate the prevalence and characterize the clinical and radiographic findings of adults whose serum alkaline phosphatase was almost always low (persistent hypophosphatasemia). We hypothesized that some of these patients might harbor previously unrecognized hypophosphatasia, a rare, inherited condition of impaired mineralization of bones and teeth. Persistent hypophosphatasemia (serum alkaline phosphatase ≤30 IU/L) was found in 1 of 1544 adult patients. These adult patients had more crystalline arthritis, orthopedic surgery, chondrocalcinosis, calcific periarthritis, enthesopathy, and diffuse idiopathic skeletal hyperostosis than a general adult patient population. A gender effect was observed. The clinical and radiographic findings of adult patients with persistent hypophosphatasemia resemble those of the adult form of hypophosphatasia. Clinicians should take notice of persistent hypophosphatasemia, consider the diagnosis of hypophosphatasia, and be cautious when considering potent anti-remodeling therapy in these adults. This population warrants further evaluation.

Keywords: HYPOPHOSPHATASEMIA; GENERAL POPULATION STUDY; HYPOPHOSPHATASIA; BISPHOSPHONATE

Links

DOI: 10.1002/jbmr.2178

PubMed: 24443354

WoS: 000340243600016

History

Received: 2013-7-15

Revised: 2014-01-14

Accepted: 2014-01-15

Online: 2014-01-20

Cited Works (1)

Year	Entry
2013	Berkseth KE, Tebben PJ, Drake MT, Hefferan TE, Jewison DE, Wermers RA. Clinical spectrum of hypophosphatasia diagnosed in adults. Bone. May 2013;54(1):21-27.

Cited By (13)

Year	Entry
2017	Whyte MP. Hypophosphatasia: an overview for 2017. Bone. September 2017;102:15-25.
2020	Schini M, Nicklin P, Eastell R. Establishing race-, gender- and age-specific reference intervals for pyridoxal 5′-phosphate in the NHANES population to better identify adult hypophosphatasia. Bone. December 2020;141:115577.
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	Salles Rosa Neto N, Englert D, McAlister WH, Mumm S, Mills D, Veis DJ, Burshell A, Boyde A, Whyte MP. Periarticular calcifications containing giant pseudo-crystals of francolite in skeletal fluorosis from 1,1-difluoroethane "huffing". Bone. July 2022;160:116421.
2023	Khursigara G, Huertas P, Wenkert D, O'Brien K, Sabbagh Y. Effects of food, fasting, and exercise on plasma pyrophosphate levels and ENPP1 activity in healthy adults. Bone. June 2023;171:116750.
2020	Bayramli R, Cevlik T, Guran T, Atay Z, Bas S, Haklar G, Bereket A, Turan S. Clinical significance of hypophosphatasemia in children. Calcif Tiss Int. June 2020;106(6):608-615.
2022	Rush ET, Johnson B, Aradhya S, Beltran D, Bristow SL, Eisenbeis S, Guerra NE, Krolczyk S, Miller N, Morales A, Ramesan P, Sarafrazi S, Truty R, Dahir K. Molecular diagnoses of X-linked and other genetic hypophosphatemias: results from a sponsored genetic testing program. J Bone Miner Res. February 2022;37(2):202-214.
2022	Soma K, Izumi M, Yamamoto Y, Miyazaki S, Watanabe K. In vitro and in vivo pharmacological profiles of DS-1211, a novel potent, selective, and orally bioavailable tissue-nonspecific alkaline phosphatase inhibitor. J Bone Miner Res. October 2022;37(10):2033-2043.
2016	Whyte MP. Hypophosphatasia: aetiology, nosology, pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. April 2016;12(4):233-246.
2017	Schmidt T, Mussawy H, Rolvien T, Hawellek T, Hubert J, Rüther W, Amling M, Barvencik F. Clinical, radiographic and biochemical characteristics of adult hypophosphatasia. Osteoporos Int. September 2017;28(9):2653-2662.
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.
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.