Bone-microarchitecture and bone-strength in a sample of adults with hypophosphatasia and a matched reference population assessed by HR-pQCT and impact microindentation

Hepp, Nicola<sup>1,2</sup>; Folkestad, Lars<sup>2,3</sup>; Møllebæk, Simone<sup>2</sup>; Frederiksen, Anja Lisbeth<sup>4,5</sup>; Duno, Morten<sup>6</sup>; Jørgensen, Niklas Rye<sup>7,8</sup>; Hermann, Anne Pernille<sup>2</sup>; Jensen, Jens-Erik Beck<sup>1,8</sup>

Affiliations

¹Dept. of Endocrinology, Copenhagen University Hospital Hvidovre, Kettegaard Alle 30, 2650 Hvidovre, Denmark

²Dept. of Endocrinology and Metabolism, Odense University Hospital, Kløvervænget 6, 5000 Odense C, Denmark

³Dept. of Clinical Research, University of Southern Denmark, Winsløwparken 19, 5000 Odense C, Denmark

⁴Dept. of Clinical Genetics, Aalborg University Hospital, Ladegaardsgade 5, 9000 Aalborg C, Denmark

⁵Dept. of Clinical Research, Aalborg University, Fredrik Bajers Vej 7K, 9220 Aalborg Ø, Denmark

⁶Dept. of Clinical Genetics, University Hospital Copenhagen Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark

⁷Dept. of Clinical Biochemistry, Rigshospitalet, Valdemar Hansens Vej 13, 2600 Glostrup, Denmark

⁸Dept. of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3 B, 2200 Copenhagen, Denmark

Abstract and keywords

Background: Hypophosphatasia (HPP) is an autosomal recessive or dominate disease affecting bone mineralization, and adults with HPP are in risk to develop metatarsal stress fractures and femoral pseudofractures. Given to the scarce data on the bone quality and its association to the fracture risk in adults with HPP, this study aimed to evaluate bone turnover, bone strength and structure in adults with HPP.

Methods: In this cross-sectional study, we included 14 adults with genetically verified HPP and 14 sex-, age-, BMI-, and menopausal status-matched reference individuals. We analyzed bone turnover markers, and measured bone material strength index (BMSi) by impact microindentation. Bone geometry, volumetric density and bone microarchitecture as well as failure load at the distal radius and tibia were evaluated using a second-generation high-resolution peripheral quantitative computed tomography system.

Results: Bone turnover markers did not differ between patients with HPP and reference individuals. BMSi did not differ between the groups (67.90 [63.75–76.00] vs 65.45 [58.43–69.55], p = 0.149). Parameters of bone geometry and volumetric density did not differ between adults with HPP and the reference group. Patients with HPP had a tendency toward higher trabecular separation (0.664 [0.613–0.724] mm vs 0.620 [0.578–0.659] mm, p = 0.054) and inhomogeneity of trabecular network (0.253 [0.235–0.283] mm vs 0.229 [0.208–0.252] mm, p = 0.056) as well as lower trabecular bone volume fraction (18.8 [16.4–22.7] % vs 22.8 [20.6–24.7] %, p = 0.054) at the distal radius. In addition, compound heterozygous adults with HPP had a significantly higher cortical porosity at the distal radius than reference individuals (1.5 [0.9–2.2] % vs 0.7 [0.6–0.7] %, p = 0.041).

Conclusions: BMSi is not reduced in adults with HPP. Increased cortical porosity may contribute to the occurrence of femoral pseudofractures in compound heterozygous adults with HPP. However, further studies investigating larger cohorts of adults with HPP using methods of bone histomorphometry are recommended to adequately assess the bone quality in adults with HPP.

Keywords: HPP; ALPL; Bone turnover; Fracture; BMSi; Bone microarchitecture

Links

DOI: 10.1016/j.bone.2022.116420

PubMed: 35421614

WoS: 000791644200002

History

Received: 2022-01-7

Revised: 2022-04-3

Accepted: 2022-04-7

Online: 2022-04-11

Cited Works (18)

Year	Entry
2015	Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the american college of medical genetics and genomics and the association for molecular pathology. Genet Med. May 2015;17(5):405-424.
2012	Pialat JB, Burghardt AJ, Sode M, Link TM, Majumdar S. Visual grading of motion induced image degradation in high resolution peripheral computed tomography: impact of image quality on measures of bone density and micro-architecture. Bone. January 2012;50(1):111-118.
2002	Pistoia W, van Rietbergen B, Lochmüller E-M, Lill CA, Eckstein F, Rüegsegger P. Estimation of distal radius failure load with micro-finite element analysis models based on three-dimensional peripheral quantitative computed tomography images. Bone. June 2002;30(6):842-848.
2020	Folkestad L, Groth KA, Shanbhogue V, Hove H, Kyhl K, Østergaard JR, Jørgensen NR, Andersen NH, Gravholt CH. Bone geometry, density, and microarchitecture in the distal radius and tibia in adults with Marfan syndrome assessed by hr‐pqct. J Bone Miner Res. December 2020;35(12):2335-2344.
2010	Burghardt AJ, Buie HR, Laib A, Majumdar S, Boyd SK. Reproducibility of direct quantitative measures of cortical bone microarchitecture of the distal radius and tibia by HR-pQCT. Bone. September 2010;47(3):519-528.
2017	Whyte MP. Hypophosphatasia: an overview for 2017. Bone. September 2017;102:15-25.
2020	Whittier DE, Boyd SK, Burghardt AJ, Paccou J, Ghasem-Zadeh A, Chapurlat R, Engelke K, Bouxsein ML. Guidelines for the assessment of bone density and microarchitecture in vivo using high-resolution peripheral quantitative computed tomography. Osteoporos Int. September 2020;31(9):1607-1627.
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.
2020	Whittier DE, Burt LA, Hanley DA, Boyd SK. Sex‐ and site‐specific reference data for bone microarchitecture in adults measured using second‐generation HR‐pQCT. J Bone Miner Res. November 2020;35(11):2151-2158.
2015	Manske SL, Zhu Y, Sandino C, Boyd SK. Human trabecular bone microarchitecture can be assessed independently of density with second generation HR-pQCT. Bone. October 2015;79:213-221.
2020	Schoeb M, Malgo F, Peeters JJM, Winter EM, Papapoulos SE, Appelman-Dijkstra NM. Treatments of osteoporosis increase bone material strength index in patients with low bone mass. Osteoporos Int. September 2020;31(9):1683-1690.
2017	Manske SL, Davison EM, Burt LA, Raymond DA, Boyd SK. The estimation of second-generation HR-pQCT from first-generation -pQCT using in vivo cross-calibration. J Bone Miner Res. July 2017;32(7):1514-1524.
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.
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.
2014	McKiernan FE, Berg RL, Fuehrer J. Clinical and radiographic findings in adults with persistent hypophosphatasemia. J Bone Miner Res. July 2014;29(7):1651-1660.
2007	Buie HR, Campbell GM, Klinck RJ, MacNeil JA, Boyd SK. Automatic segmentation of cortical and trabecular compartments based on a dual threshold technique for in vivo micro-CT bone analysis. Bone. October 2007;41(4):505-515.
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.
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.