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Published in: Osteoporosis International 8/2013

01-08-2013 | Original Article

High bone mineral apparent density in children with X-linked hypophosphatemia

Authors: S. S. Beck-Nielsen, K. Brixen, J. Gram, C. Mølgaard

Published in: Osteoporosis International | Issue 8/2013

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Abstract

Summary

Bone mineral apparent density (BMAD) in children with X-linked hypophosphatemia (XLH) was evaluated, as they are unlikely to have extra-skeletal ossifications contributing to the elevated bone mineral density of the spine in adult patients. Children with XLH also had significantly higher BMAD of the spine compared to femoral neck.

Introduction

BMAD obtained by dual-energy X-ray absorptiometry scans in children with XLH was evaluated, as they are unlikely to have the extra-skeletal ossifications contributing to the elevated bone mineral density of the spine in adult patients.

Methods

A total of 15 children with biochemically and genetically verified XLH were recruited. Anthropometric measurements were performed, and to correct for the short stature (small bones), the BMAD of the spine and the femoral neck was evaluated.

Results

Z-scores of BMAD of the spine (mean (95 % CI); 2.0 (1.3–2.7); p < 0.001) were significantly elevated compared to reference children. Z-scores of the femoral neck (1.0 (−0.0 to 2.1); p = 0.059) tended to be elevated. Spine Z-scores were significantly higher than the Z-scores of the femoral neck, (paired t test, p = 0.02). BMAD of the spine was evaluated according to the Molgaard’s approach; XLH children had normal bone size of the spine for age due to a normal sitting height Z-score of −0.4 (−1.0 to 0.1); p = 0.1. Z-scores of bone mineral content (BMC) of the spine for bone area were elevated (1.4 (0.8–2.1); p < 0.001). No reference data were available to allow evaluation of the BMAD of the femoral neck by the Molgaard's approach.

Conclusions

Children with XLH have an increased BMAD and a high BMC for bone area at the lumbar spine, and this was due to causes other than extra-skeletal ossifications and corrected for bone size. The BMAD of the spine was significantly higher compared to the femoral neck.
Literature
1.
go back to reference Beck-Nielsen SS, Brock-Jacobsen B, Gram J, Brixen K, Jensen TK (2009) Incidence and prevalence of nutritional and hereditary rickets in southern Denmark. Eur J Endocrinol 160:491–497PubMedCrossRef Beck-Nielsen SS, Brock-Jacobsen B, Gram J, Brixen K, Jensen TK (2009) Incidence and prevalence of nutritional and hereditary rickets in southern Denmark. Eur J Endocrinol 160:491–497PubMedCrossRef
2.
go back to reference Beck-Nielsen SS, Brixen K, Gram J, Brusgaard K (2012) Mutational analysis of PHEX, FGF23, DMP1, SLC34A3 and CLCN5 in patients with hypophosphatemic rickets. J Hum Genet 57:453–458PubMedCrossRef Beck-Nielsen SS, Brixen K, Gram J, Brusgaard K (2012) Mutational analysis of PHEX, FGF23, DMP1, SLC34A3 and CLCN5 in patients with hypophosphatemic rickets. J Hum Genet 57:453–458PubMedCrossRef
3.
go back to reference Carpenter TO (2012) The expanding family of hypophosphatemic syndromes. J Bone Miner Metab 30:1–9PubMedCrossRef Carpenter TO (2012) The expanding family of hypophosphatemic syndromes. J Bone Miner Metab 30:1–9PubMedCrossRef
5.
go back to reference Seeman E (1998) Growth in bone mass and size—are racial and gender differences in bone mineral density more apparent than real? J Clin Endocrinol Metab 83:1414–1419PubMedCrossRef Seeman E (1998) Growth in bone mass and size—are racial and gender differences in bone mineral density more apparent than real? J Clin Endocrinol Metab 83:1414–1419PubMedCrossRef
6.
go back to reference Rauch F, Schoenau E (2001) Changes in bone density during childhood and adolescence: an approach based on bone's biological organization. J Bone MinerRes 16:597–604CrossRef Rauch F, Schoenau E (2001) Changes in bone density during childhood and adolescence: an approach based on bone's biological organization. J Bone MinerRes 16:597–604CrossRef
7.
go back to reference Binkovitz LA, Henwood MJ (2007) Pediatric DXA: technique and interpretation. Pediatr Radiol 37:21–31PubMedCrossRef Binkovitz LA, Henwood MJ (2007) Pediatric DXA: technique and interpretation. Pediatr Radiol 37:21–31PubMedCrossRef
8.
go back to reference Carter DR, Bouxsein ML, Marcus R (1992) New approaches for interpreting projected bone densitometry data. J Bone Miner Res 7:137–145PubMedCrossRef Carter DR, Bouxsein ML, Marcus R (1992) New approaches for interpreting projected bone densitometry data. J Bone Miner Res 7:137–145PubMedCrossRef
9.
go back to reference Molgaard C, Thomsen BL, Prentice A, Cole TJ, Michaelsen KF (1997) Whole body bone mineral content in healthy children and adolescents. Arch Dis Child 76:9–15PubMedCrossRef Molgaard C, Thomsen BL, Prentice A, Cole TJ, Michaelsen KF (1997) Whole body bone mineral content in healthy children and adolescents. Arch Dis Child 76:9–15PubMedCrossRef
10.
go back to reference Ward KA, Ashby RL, Roberts SA, Adams JE, Zulf MM (2007) UK reference data for the Hologic QDR Discovery dual-energy X-ray absorptiometry scanner in healthy children and young adults aged 6–17 years. Arch Dis Child 92:53–59PubMedCrossRef Ward KA, Ashby RL, Roberts SA, Adams JE, Zulf MM (2007) UK reference data for the Hologic QDR Discovery dual-energy X-ray absorptiometry scanner in healthy children and young adults aged 6–17 years. Arch Dis Child 92:53–59PubMedCrossRef
11.
go back to reference Beck-Nielsen SS, Brusgaard K, Rasmussen LM et al (2010) Phenotype presentation of hypophosphatemic rickets in adults. Calcif Tissue Int 87:108–119PubMedCrossRef Beck-Nielsen SS, Brusgaard K, Rasmussen LM et al (2010) Phenotype presentation of hypophosphatemic rickets in adults. Calcif Tissue Int 87:108–119PubMedCrossRef
12.
go back to reference Rosenthall L (1993) DEXA bone densitometry measurements in adults with X-linked hypophosphatemia. Clin Nucl Med 18:564–566PubMedCrossRef Rosenthall L (1993) DEXA bone densitometry measurements in adults with X-linked hypophosphatemia. Clin Nucl Med 18:564–566PubMedCrossRef
13.
go back to reference Reid IR, Murphy WA, Hardy DC, Teitelbaum SL, Bergfeld MA, Whyte MP (1991) X-linked hypophosphatemia: skeletal mass in adults assessed by histomorphometry, computed tomography, and absorptiometry. Am J Med 90:63–69PubMedCrossRef Reid IR, Murphy WA, Hardy DC, Teitelbaum SL, Bergfeld MA, Whyte MP (1991) X-linked hypophosphatemia: skeletal mass in adults assessed by histomorphometry, computed tomography, and absorptiometry. Am J Med 90:63–69PubMedCrossRef
14.
go back to reference Baroncelli GI, Bertelloni S, Ceccarelli C, Saggese G (2001) Effect of growth hormone treatment on final height, phosphate metabolism, and bone mineral density in children with X-linked hypophosphatemic rickets. J Pediatr 138:236–243PubMedCrossRef Baroncelli GI, Bertelloni S, Ceccarelli C, Saggese G (2001) Effect of growth hormone treatment on final height, phosphate metabolism, and bone mineral density in children with X-linked hypophosphatemic rickets. J Pediatr 138:236–243PubMedCrossRef
15.
go back to reference Oliveri MB, Cassinelli H, Bergada C, Mautalen CA (1991) Bone mineral density of the spine and radius shaft in children with X-linked hypophosphatemic rickets (XLH). Bone Miner 12:91–100PubMedCrossRef Oliveri MB, Cassinelli H, Bergada C, Mautalen CA (1991) Bone mineral density of the spine and radius shaft in children with X-linked hypophosphatemic rickets (XLH). Bone Miner 12:91–100PubMedCrossRef
16.
go back to reference Shore RM, Langman CB, Poznanski AK (2000) Lumbar and radial bone mineral density in children and adolescents with X-linked hypophosphatemia: evaluation with dual X-ray absorptiometry. Skeletal Radiol 29:90–93PubMedCrossRef Shore RM, Langman CB, Poznanski AK (2000) Lumbar and radial bone mineral density in children and adolescents with X-linked hypophosphatemia: evaluation with dual X-ray absorptiometry. Skeletal Radiol 29:90–93PubMedCrossRef
17.
go back to reference Baroncelli GI, Federico G, Bertelloni S, Sodini F, De TF, Cadossi R, Saggese G (2003) Assessment of bone quality by quantitative ultrasound of proximal phalanges of the hand and fracture rate in children and adolescents with bone and mineral disorders. Pediatr Res 54:125–136PubMedCrossRef Baroncelli GI, Federico G, Bertelloni S, Sodini F, De TF, Cadossi R, Saggese G (2003) Assessment of bone quality by quantitative ultrasound of proximal phalanges of the hand and fracture rate in children and adolescents with bone and mineral disorders. Pediatr Res 54:125–136PubMedCrossRef
18.
go back to reference Block JE, Piel CF, Selvidge R, Genant HK (1989) Familial hypophosphatemic rickets: bone mass measurements in children following therapy with calcitriol and supplemental phosphate. Calcif Tissue Int 44:86–92PubMedCrossRef Block JE, Piel CF, Selvidge R, Genant HK (1989) Familial hypophosphatemic rickets: bone mass measurements in children following therapy with calcitriol and supplemental phosphate. Calcif Tissue Int 44:86–92PubMedCrossRef
19.
go back to reference Saggese G, Baroncelli GI, Bertelloni S, Perri G (1995) Long-term growth hormone treatment in children with renal hypophosphatemic rickets: effects on growth, mineral metabolism, and bone density. J Pediatr 127:395–402PubMedCrossRef Saggese G, Baroncelli GI, Bertelloni S, Perri G (1995) Long-term growth hormone treatment in children with renal hypophosphatemic rickets: effects on growth, mineral metabolism, and bone density. J Pediatr 127:395–402PubMedCrossRef
20.
go back to reference Andersen E, Hutchings B, Jansen J, Nyholm M (1982) Heights and weights of Danish children. Ugeskr Laeger 144:1760–1765PubMed Andersen E, Hutchings B, Jansen J, Nyholm M (1982) Heights and weights of Danish children. Ugeskr Laeger 144:1760–1765PubMed
21.
go back to reference Hertel NT, Scheike T, Juul A, Main KM, Holm K, Bach-Mortensen N, Skakkebaek NE, Muller JR (1995) Body proportions of Danish children. Curves for sitting height ratio, subischial length and arm span. Ugeskr Laeger 157:6876–6881PubMed Hertel NT, Scheike T, Juul A, Main KM, Holm K, Bach-Mortensen N, Skakkebaek NE, Muller JR (1995) Body proportions of Danish children. Curves for sitting height ratio, subischial length and arm span. Ugeskr Laeger 157:6876–6881PubMed
22.
go back to reference McNair SL, Stickler GB (1969) Growth in familial hypophosphatemic vitamin-D-resistant rickets. N Engl J Med 281:512–516PubMedCrossRef McNair SL, Stickler GB (1969) Growth in familial hypophosphatemic vitamin-D-resistant rickets. N Engl J Med 281:512–516PubMedCrossRef
23.
go back to reference Steendijk R, Herweijer TJ (1984) Height, sitting height and leg length in patients with hypophosphataemic rickets. Acta Paediatr Scand 73:181–184PubMedCrossRef Steendijk R, Herweijer TJ (1984) Height, sitting height and leg length in patients with hypophosphataemic rickets. Acta Paediatr Scand 73:181–184PubMedCrossRef
24.
go back to reference Zivicnjak M, Schnabel D, Billing H et al (2011) Age-related stature and linear body segments in children with X-linked hypophosphatemic rickets. Pediatr Nephrol 26:223–231PubMedCrossRef Zivicnjak M, Schnabel D, Billing H et al (2011) Age-related stature and linear body segments in children with X-linked hypophosphatemic rickets. Pediatr Nephrol 26:223–231PubMedCrossRef
25.
go back to reference Glorieux FH, Marie PJ, Pettifor JM, Delvin EE (1980) Bone response to phosphate salts, ergocalciferol, and calcitriol in hypophosphatemic vitamin D-resistant rickets. N Engl J Med 303:1023–1031PubMedCrossRef Glorieux FH, Marie PJ, Pettifor JM, Delvin EE (1980) Bone response to phosphate salts, ergocalciferol, and calcitriol in hypophosphatemic vitamin D-resistant rickets. N Engl J Med 303:1023–1031PubMedCrossRef
26.
go back to reference Sullivan W, Carpenter T, Glorieux F, Travers R, Insogna K (1992) A prospective trial of phosphate and 1,25-dihydroxyvitamin D3 therapy in symptomatic adults with X-linked hypophosphatemic rickets. J Clin Endocrinol Metab 75:879–885PubMedCrossRef Sullivan W, Carpenter T, Glorieux F, Travers R, Insogna K (1992) A prospective trial of phosphate and 1,25-dihydroxyvitamin D3 therapy in symptomatic adults with X-linked hypophosphatemic rickets. J Clin Endocrinol Metab 75:879–885PubMedCrossRef
27.
go back to reference Rauch F (2006) Material matters: a mechanostat-based perspective on bone development in osteogenesis imperfecta and hypophosphatemic rickets. J Musculoskelet Neuronal Interact 6:142–146PubMed Rauch F (2006) Material matters: a mechanostat-based perspective on bone development in osteogenesis imperfecta and hypophosphatemic rickets. J Musculoskelet Neuronal Interact 6:142–146PubMed
28.
go back to reference Frost HM (2003) Bone's mechanostat: a 2003 update. Anat Rec A Discov Mol Cell Evol Biol 275:1081–1101PubMedCrossRef Frost HM (2003) Bone's mechanostat: a 2003 update. Anat Rec A Discov Mol Cell Evol Biol 275:1081–1101PubMedCrossRef
29.
go back to reference Reusz GS, Miltenyi G, Stubnya G, Szabo A, Horvath C, Byrd DJ, Peter F, Tulassay T (1997) X-linked hypophosphatemia: effects of treatment with recombinant human growth hormone. Pediatr Nephrol 11:573–577PubMedCrossRef Reusz GS, Miltenyi G, Stubnya G, Szabo A, Horvath C, Byrd DJ, Peter F, Tulassay T (1997) X-linked hypophosphatemia: effects of treatment with recombinant human growth hormone. Pediatr Nephrol 11:573–577PubMedCrossRef
30.
go back to reference Faulkner RA, Bailey DA, Drinkwater DT, McKay HA, Arnold C, Wilkinson AA (1996) Bone densitometry in Canadian children 8–17 years of age. Calcif Tissue Int 59:344–351PubMedCrossRef Faulkner RA, Bailey DA, Drinkwater DT, McKay HA, Arnold C, Wilkinson AA (1996) Bone densitometry in Canadian children 8–17 years of age. Calcif Tissue Int 59:344–351PubMedCrossRef
31.
go back to reference Kroger H, Kotaniemi A, Vainio P, Alhava E (1992) Bone densitometry of the spine and femur in children by dual-energy X-ray absorptiometry. Bone Miner 17:75–85PubMedCrossRef Kroger H, Kotaniemi A, Vainio P, Alhava E (1992) Bone densitometry of the spine and femur in children by dual-energy X-ray absorptiometry. Bone Miner 17:75–85PubMedCrossRef
32.
go back to reference Katzman DK, Bachrach LK, Carter DR, Marcus R (1991) Clinical and anthropometric correlates of bone mineral acquisition in healthy adolescent girls. J Clin Endocrinol Metab 73:1332–1339PubMedCrossRef Katzman DK, Bachrach LK, Carter DR, Marcus R (1991) Clinical and anthropometric correlates of bone mineral acquisition in healthy adolescent girls. J Clin Endocrinol Metab 73:1332–1339PubMedCrossRef
33.
go back to reference Berndt M, Ehrich JH, Lazovic D et al (1996) Clinical course of hypophosphatemic rickets in 23 adults. Clin Nephrol 45:33–41PubMed Berndt M, Ehrich JH, Lazovic D et al (1996) Clinical course of hypophosphatemic rickets in 23 adults. Clin Nephrol 45:33–41PubMed
34.
go back to reference Hardy DC, Murphy WA, Siegel BA, Reid IR, Whyte MP (1989) X-linked hypophosphatemia in adults: prevalence of skeletal radiographic and scintigraphic features. Radiology 171:403–414PubMed Hardy DC, Murphy WA, Siegel BA, Reid IR, Whyte MP (1989) X-linked hypophosphatemia in adults: prevalence of skeletal radiographic and scintigraphic features. Radiology 171:403–414PubMed
35.
go back to reference Strom TM, Francis F, Lorenz B, Boddrich A, Econs MJ, Lehrach H, Meitinger T (1997) Pex gene deletions in Gy and Hyp mice provide mouse models for X-linked hypophosphatemia. Hum Mol Genet 6:165–171PubMedCrossRef Strom TM, Francis F, Lorenz B, Boddrich A, Econs MJ, Lehrach H, Meitinger T (1997) Pex gene deletions in Gy and Hyp mice provide mouse models for X-linked hypophosphatemia. Hum Mol Genet 6:165–171PubMedCrossRef
36.
go back to reference Li H, Martin A, David V, Quarles LD (2011) Compound deletion of Fgfr3 and Fgfr4 partially rescues the Hyp mouse phenotype. Am J Physiol Endocrinol Metab 300:E508–E517PubMedCrossRef Li H, Martin A, David V, Quarles LD (2011) Compound deletion of Fgfr3 and Fgfr4 partially rescues the Hyp mouse phenotype. Am J Physiol Endocrinol Metab 300:E508–E517PubMedCrossRef
37.
go back to reference Reid IR, Hardy DC, Murphy WA, Teitelbaum SL, Bergfeld MA, Whyte MP (1989) X-linked hypophosphatemia: a clinical, biochemical, and histopathologic assessment of morbidity in adults. Medicine (Baltimore) 68:336–352 Reid IR, Hardy DC, Murphy WA, Teitelbaum SL, Bergfeld MA, Whyte MP (1989) X-linked hypophosphatemia: a clinical, biochemical, and histopathologic assessment of morbidity in adults. Medicine (Baltimore) 68:336–352
38.
go back to reference Marie PJ, Glorieux FH (1981) Stimulation of cortical bone mineralization and remodeling by phosphate and 1,25-dihydroxyvitamin D in vitamin D-resistant rickets. Metab Bone Dis Relat Res 3:159–164PubMedCrossRef Marie PJ, Glorieux FH (1981) Stimulation of cortical bone mineralization and remodeling by phosphate and 1,25-dihydroxyvitamin D in vitamin D-resistant rickets. Metab Bone Dis Relat Res 3:159–164PubMedCrossRef
39.
go back to reference Harrison JE, Cumming WA, Fornasier V, Fraser D, Kooh SW, McNeill KG (1976) Increased bone mineral content in young adults with familial hypophosphatemic vitamin D refractory rickets. Metabolism 25:33–40PubMedCrossRef Harrison JE, Cumming WA, Fornasier V, Fraser D, Kooh SW, McNeill KG (1976) Increased bone mineral content in young adults with familial hypophosphatemic vitamin D refractory rickets. Metabolism 25:33–40PubMedCrossRef
40.
go back to reference Marie PJ, Glorieux FH (1981) Histomorphometric study of bone remodeling in hypophosphatemic vitamin D-resistant rickets. Metab Bone Dis Relat Res 3:31–38PubMedCrossRef Marie PJ, Glorieux FH (1981) Histomorphometric study of bone remodeling in hypophosphatemic vitamin D-resistant rickets. Metab Bone Dis Relat Res 3:31–38PubMedCrossRef
41.
go back to reference Carpenter TO, Imel EA, Holm IA, Jan de Beur SM, Insogna KL (2011) A clinician's guide to X-linked hypophosphatemia. J Bone Miner Res 26:1381–1388PubMedCrossRef Carpenter TO, Imel EA, Holm IA, Jan de Beur SM, Insogna KL (2011) A clinician's guide to X-linked hypophosphatemia. J Bone Miner Res 26:1381–1388PubMedCrossRef
42.
go back to reference Marie PJ, Travers R, Glorieux FH (1981) Healing of rickets with phosphate supplementation in the hypophosphatemic male mouse. J Clin Invest 67:911–914PubMedCrossRef Marie PJ, Travers R, Glorieux FH (1981) Healing of rickets with phosphate supplementation in the hypophosphatemic male mouse. J Clin Invest 67:911–914PubMedCrossRef
43.
go back to reference Bianchi ML, Baim S, Bishop NJ, Gordon CM, Hans DB, Langman CB, Leonard MB, Kalkwarf HJ (2010) Official positions of the International Society for Clinical Densitometry (ISCD) on DXA evaluation in children and adolescents. Pediatr Nephrol 25:37–47PubMedCrossRef Bianchi ML, Baim S, Bishop NJ, Gordon CM, Hans DB, Langman CB, Leonard MB, Kalkwarf HJ (2010) Official positions of the International Society for Clinical Densitometry (ISCD) on DXA evaluation in children and adolescents. Pediatr Nephrol 25:37–47PubMedCrossRef
44.
go back to reference Zemel BS, Leonard MB, Kelly A et al (2010) Height adjustment in assessing dual energy X-ray absorptiometry measurements of bone mass and density in children. J Clin Endocrinol Metab 95:1265–1273PubMedCrossRef Zemel BS, Leonard MB, Kelly A et al (2010) Height adjustment in assessing dual energy X-ray absorptiometry measurements of bone mass and density in children. J Clin Endocrinol Metab 95:1265–1273PubMedCrossRef
Metadata
Title
High bone mineral apparent density in children with X-linked hypophosphatemia
Authors
S. S. Beck-Nielsen
K. Brixen
J. Gram
C. Mølgaard
Publication date
01-08-2013
Publisher
Springer London
Published in
Osteoporosis International / Issue 8/2013
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-013-2286-9

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