ORIGINAL PAPER
Bone metabolism in patients with mucopolysaccharidosis type II
Submission date: 2014-07-25
Final revision date: 2014-11-17
Acceptance date: 2014-11-19
Online publication date: 2014-11-29
Publication date: 2014-12-31
Reumatologia 2014;52(6):354-361
KEYWORDS
TOPICS
ABSTRACT
Objectives: To assess different parameters of bone metabolism in patients with mucopolysaccharidosis type II (MPS II) to better comprehend the mechanisms responsible for their skeletal pathology.
Material and methods: In MPS type II patients (n = 7, age 4–28 years, mean 11.6, median 7) bone metabolism was assessed using the following: a) parameters of calcium-phosphate metabolism (serum level of calcium, phosphorus, alkaline phosphatase (ALP), parathormone (PTH), and vitamin 25(OH)D), b) parameters of bone formation (osteocalcin) and resorption (B-crossLaps), c) bone mineral density (BMD) of the lumbar spine assessed by dual-energy X-ray absorptiometry (DXA), and d) radiographs of the skeletal system.
Results: All patients were normocalcemic, but the majority of them had abnormal serum levels of other parameters of calcium-phosphate metabolism such as: hypophosphatemia (4/7), decreased ALP (2/7), increased PTH (4/7), and vitamin 25(OH)D deficiency (6/7), which in 3 patients was associated with secondary hyperparathyroidism. Five patients presented increased levels of osteocalcin in the serum, and all the patients had high levels of β-CTx. Two adult patients had osteoporosis (T-scores –3.9 and –5.7), while in 3 pediatric patients the Z-score was within the normal range. Radiographs of bones revealed signs of dysostosis multiplex typical for MPS disease in all patients, and in adult patients they corresponded to BMD.
Conclusions: 1. MPS II patients have disturbed serum parameters of bone health and therefore may be at a higher risk for osteoporosis or osteomalacia. 2. Supplementation with vitamin D may be required in MPS patients.
Material and methods: In MPS type II patients (n = 7, age 4–28 years, mean 11.6, median 7) bone metabolism was assessed using the following: a) parameters of calcium-phosphate metabolism (serum level of calcium, phosphorus, alkaline phosphatase (ALP), parathormone (PTH), and vitamin 25(OH)D), b) parameters of bone formation (osteocalcin) and resorption (B-crossLaps), c) bone mineral density (BMD) of the lumbar spine assessed by dual-energy X-ray absorptiometry (DXA), and d) radiographs of the skeletal system.
Results: All patients were normocalcemic, but the majority of them had abnormal serum levels of other parameters of calcium-phosphate metabolism such as: hypophosphatemia (4/7), decreased ALP (2/7), increased PTH (4/7), and vitamin 25(OH)D deficiency (6/7), which in 3 patients was associated with secondary hyperparathyroidism. Five patients presented increased levels of osteocalcin in the serum, and all the patients had high levels of β-CTx. Two adult patients had osteoporosis (T-scores –3.9 and –5.7), while in 3 pediatric patients the Z-score was within the normal range. Radiographs of bones revealed signs of dysostosis multiplex typical for MPS disease in all patients, and in adult patients they corresponded to BMD.
Conclusions: 1. MPS II patients have disturbed serum parameters of bone health and therefore may be at a higher risk for osteoporosis or osteomalacia. 2. Supplementation with vitamin D may be required in MPS patients.
REFERENCES (29)
1.
Neufeld EF, Muenzer J. The mucopolysaccharidoses. In: The metabolic and molecular basis of inherited disease. Scriver CR, Beaudet AL, Sly WS (eds.). McGraw-Hill, New York 2001; 3421-3452. .
2.
Nelson J, Crowhurst J, Carey B, Greed L. Incidence of the mucopolysaccharidoses in Western Australia. Am J Med Genet A 2003; 123A: 310-313. .
3.
Baehner F, Schmiedeskamp C, Krummenauer F, et al. Cumulative incidence rates of the mucopolysaccharidoses in Germany. J Inherit Metab Dis 2005; 28: 1011-1017. .
4.
Jurecka A, Krumina Z, Żuber Z, et al. Mucopolysaccharidosis type II in females and response to enzyme replacement therapy. Am J Med Genet A 2012; 158A: 450-454. .
5.
Scarpa M, Almássy Z, Beck M, Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease. Orphanet J Rare Dis 2011; 6: 72. .
6.
Simonaro CM, D’Angelo M, Haskins ME, Schuchman EH. Joint and bone disease in mucopolysaccharidoses VI and VII: identification of new therapeutic targets and biomarkers using animal models. Pediatr Res 2005; 57: 701-707. .
7.
Simonaro CM, D’Angelo M, He X, et al. Mechanism of glycosaminoglycan-mediated bone and joint disease: implications for the mucopolysaccharidoses and other connective tissue diseases. Am J Pathol 2008; 172: 112-122. .
8.
Chiaro JA, Baron MD, Del Alcazar CM, et al. Postnatal progression of bone disease in the cervical spines of mucopolysaccharidosis I dogs. Bone 2013; 55: 78-83. .
9.
Polgreen LE, Thomas W, Fung E, et al. Low bone mineral content and challenges in interpretation of dual-energy X-ray absorptiometry in children withmucopolysaccharidosis types I, II, and VI. J Clin Densitom 2014; 17: 200-206. .
10.
Fung EB, Johnson JA, Madden J, et al. Bone density assessment in patients with mucopolysaccharidosis: A preliminary report from patients with MPS II and VI. J Pediatr Rehabil Med 2010; 3: 13-23. .
11.
Rigante D, Caradonna P. Secondary skeletal involvement in Sanfilippo syndrome. QJM 2004; 97: 205-209. .
12.
Oussoren E, Brands MM, Ruijter GJ, et al. Bone, joint and tooth development in mucopolysaccharidoses: Relevance to therapeutic options. Biochim Biophys Acta 2011; 1812: 1542-1556. .
13.
Kachur E, Del Maestro R. Mucopolysaccharidoses and spinal cord compression: case report and review of the literature with implications of bone marrow transplantation. Neurosurgery 2000; 47: 223-228. .
14.
Weisstein JS, Delgado E, Steinbach LS, et al. Musculoskeletal manifestations of Hurler syndrome: long-term follow-up after bone marrow transplantation. J Pediatr Orthop 2004; 24: 97-101. .
15.
Sifuentes M, Doroshow R, Hoft R, et al. A follow-up study of MPS I patients treated with laronidase enzyme replacement therapy for 6 years. Mol Genet Metab 2007; 90: 171-180. .
16.
Jurecka A, Marucha J, Jurkiewicz E, et al. Enzyme replacement therapy in an attenuated case of mucopolysaccharidosis type I (Scheie syndrome): a 6.5-year detailed follow-up. Pediatr Neurol 2012; 47: 461-465. .
17.
Żuber Z, Różdżyńska-Świątkowska A, Jurecka A, Tylki-Szymańska A. The effect of recombinant human iduronate-2-sulfatase (Idursulfase) on growth in young patients with mucopolysaccharidosis type II. PLoS One 2014; 9: e85074. .
19.
Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 2011; 96: 53-58. .
20.
Uziel Y, Zifman E, Hashkes PJ. Osteoporosis in children: pediatric and pediatric rheumatology perspective: a review. Pediatr Rheumatol Online J 2009; 7: 16. .
21.
Zemel BS, Leonard MB, Kelly A, et al. Height adjustment in assessing dual energy X-ray absorptiometry measurements of bone mass and density in children. J Clin Endocrinol Metab 2010; 95: 1265-1273. .
22.
Green JJ, Robinson DA, Wilson GE, et al. Calcitriol modulation of cardiac contractile performance via protein kinase C. J Mol Cell Cardiol 2006; 41: 350-359. .
23.
Brehm JM1, Schuemann B, Fuhlbrigge AL, et al. Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study. J Allergy Clin Immunol 2010; 126: 52-58.e5. .
24.
Jeng L, Yamshchikov AV, Judd SE, et al. Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis. J Transl Med 2009; 7: 28. .
25.
Fromigué O, Marie PJ, Lomri A. Differential effects of transforming growth factor beta2, dexamethasone and 1,25-dihydroxyvitamin D on humanbone marrow stromal cells. Cytokine 1997; 9: 613-623. .
26.
Lin HY, Shih SC, Chuang CK, et al. Assessment of bone mineral density by dual energy x-ray absorptiometry in patients with mucopolysaccharidoses. Orphanet J Rare Dis 2013; 8: 71. .
27.
Peacock M. Osteomalacia and rickets. In: Metabolic bone and stone disease. Nordin B, Need A, Morris H (eds.). Livingstone, London 1993; 83-118. .
28.
Guevarra MS, Yeh JK, Castro Magana M, Aloia JF. Synergistic effect of parathyroid hormone and growth hormone on trabecular and cortical bone formation in hypophysectomized rats. Horm Res Paediatr 2010; 73: 248-257. .
29.
Maïmoun L, Sultan C. Effects of physical activity on bone remodeling. Metabolism 2011; 60: 373-388.
Copyright: © Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie. This is an Open Access journal, all articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (https://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Share
RELATED ARTICLE
| eISSN: | 2084-9834 |
| ISSN: | 0034-6233 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
