Metabolic Bone Diseases in the Pediatric Population

Abstract

Bone plays an important role in regulating mineral balance in response to physiologic needs. In addition, bone is subject to a continuous remodeling process to maintain healthy bone mass and growth. Metabolic bone diseases are a heterogeneous group of diseases caused by abnormalities of bone mass, mineral structure homeostasis, bone turnover, or bone growth. In pediatrics, several significant advances have been made in recent years in the diagnosis of metabolic bone diseases (e.g., osteogenesis imperfecta, hyperparathyroidism, rickets, renal osteodystrophy, pediatric osteoporosis, and osteopetrosis). Imaging is fundamental in the diagnosis of these pathologies.

Keywords

bone metabolism - osteogenesis imperfecta - hyperparathyroidism - rickets - pediatric osteoporosis

Publication History

Article published online:
21 May 2021

• References

• 1 Malcolm AJ. Metabolic bone disease. Curr Diagn Pathol 2002; 8 (01) 19-25
• 2 Beyens G, Van Hul W. Pathophysiology and genetics of metabolic bone disorders characterized by increased bone turnover. Crit Rev Eukaryot Gene Expr 2007; 17 (03) 215-240
• 3 Jilka RL. Biology of the basic multicellular unit and the pathophysiology of osteoporosis. Med Pediatr Oncol 2003; 41 (03) 182-185
• 4 Raggatt LJ, Partridge NC. Cellular and molecular mechanisms of bone remodeling. J Biol Chem 2010; 285 (33) 25103-25108
• 5 Gómez-Alonso C. Paediatric metabolic bone disease: a lifetime ahead. Adv Ther 2020; 37 (Suppl. 02) 38-46
• 6 Forlino A, Marini JC. Osteogenesis imperfecta. Lancet 2016; 387 (10028): 1657-1671
• 7 Marini JC, Reich A, Smith SM. Osteogenesis imperfecta due to mutations in non-collagenous genes: lessons in the biology of bone formation. Curr Opin Pediatr 2014; 26 (04) 500-507
• 8 Barnes AM, Chang W, Morello R. et al. Deficiency of cartilage-associated protein in recessive lethal osteogenesis imperfecta. N Engl J Med 2006; 355 (26) 2757-2764
• 9 Harrington J, Sochett E, Howard A. Update on the evaluation and treatment of osteogenesis imperfecta. Pediatr Clin North Am 2014; 61 (06) 1243-1257
• 10 Cohen JS. Patterns of inheritance in osteogenesis imperfecta. In: Shapiro JR, Byers PH, Glorieux FH, Sponseller PD. eds. Osteogenesis Imperfecta: A Translational Approach to Brittle Bone Disease. New York, NY: Elsevier; 2013: 99
• 11 Sillence DO, Rimoin DL, Danks DM. Clinical variability in osteogenesis imperfecta—variable expressivity or genetic heterogeneity. Birth Defects Orig Artic Ser 1979; 15 (5B) 113-129
• 12 Willing MC, Deschenes SP, Scott DA. et al. Osteogenesis imperfecta type I: molecular heterogeneity for COL1A1 null alleles of type I collagen. Am J Hum Genet 1994; 55 (04) 638-647
• 13 Van Dijk FS, Sillence DO. Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment. Am J Med Genet A 2014; 164A [phone] Published correction appears in Am J Med Genet A 2015;167A(5):1178
• 14 El Demellawy D, Davila J, Shaw A, Nasr Y. Brief review on metabolic bone disease. Acad Forensic Pathol 2018; 8 (03) 611-640
• 15 Glorieux FH, Rauch F, Plotkin H. et al. Type V osteogenesis imperfecta: a new form of brittle bone disease. J Bone Miner Res 2000; 15 (09) 1650-1658
• 16 Laine CM, Joeng KS, Campeau PM. et al. WNT1 mutations in early-onset osteoporosis and osteogenesis imperfecta. N Engl J Med 2013; 368 (19) 1809-1816
• 17 Kang H, Aryal A C S, Marini JC. Osteogenesis imperfecta: new genes reveal novel mechanisms in bone dysplasia. Transl Res 2017; 181: 27-48
• 18 Palomo T, Vilaça T, Lazaretti-Castro M. Osteogenesis imperfecta: diagnosis and treatment. Curr Opin Endocrinol Diabetes Obes 2017; 24 (06) 381-388
• 19 Fotiadou AN, Calleja M, Hargunani R, Keen R. Skeletal manifestations of osteogenesis imperfecta. Semin Musculoskelet Radiol 2016; 20 (03) 279-286
• 20 Ben Amor IM, Roughley P, Glorieux FH, Rauch F. Skeletal clinical characteristics of osteogenesis imperfecta caused by haploinsufficiency mutations in COL1A1. J Bone Miner Res 2013; 28 (09) 2001-2007
• 21 Zionts LE, Moon CN. Olecranon apophysis fractures in children with osteogenesis imperfecta revisited. J Pediatr Orthop 2002; 22 (06) 745-750
• 22 Rauch F, Plotkin H, Zeitlin L, Glorieux FH. Bone mass, size, and density in children and adolescents with osteogenesis imperfecta: effect of intravenous pamidronate therapy. J Bone Miner Res 2003; 18 (04) 610-614
• 23 Chang CY, Rosenthal DI, Mitchell DM, Handa A, Kattapuram SV, Huang AJ. Imaging findings of metabolic bone disease. Radiographics 2016; 36 (06) 1871-1887
• 24 Khan A, Bilezikian J. Primary hyperparathyroidism: pathophysiology and impact on bone. CMAJ 2000; 163 (02) 184-187
• 25 Bhadada SK, Bhansali A, Dutta P, Behera A, Chanukya GV, Mittal BR. Characteristics of primary hyperparathyroidism in adolescents. J Pediatr Endocrinol Metab 2008; 21 (12) 1147-1153
• 26 Starker LF, Akerström T, Long WD. et al. Frequent germ-line mutations of the MEN1, CASR, and HRPT2/CDC73 genes in young patients with clinically non-familial primary hyperparathyroidism. Horm Cancer 2012; 3 (1-2): 44-51
• 27 Roizen J, Levine MA. Primary hyperparathyroidism in children and adolescents. J Chin Med Assoc 2012; 75 (09) 425-434
• 28 Murphey MD, Sartoris DJ, Quale JL, Pathria MN, Martin NL. Musculoskeletal manifestations of chronic renal insufficiency. Radiographics 1993; 13 (02) 357-379
• 29 Fraser WD. Hyperparathyroidism. Lancet 2009; 374 (9684): 145-158
• 30 Treglia G, Annunziata S, Pizzuto DA, Giovanella L, Prior JO, Ceriani L. Detection rate of ¹⁸F-labeled PSMA PET/CT in biochemical recurrent prostate cancer: a systematic review and a meta-analysis. Cancers (Basel) 2019; 11 (05) 710
• 31 Cristina EV, Alberto F. Management of familial hyperparathyroidism syndromes: MEN1, MEN2, MEN4, HPT-Jaw tumour, familial isolated hyperparathyroidism, FHH, and neonatal severe hyperparathyroidism. Best Pract Res Clin Endocrinol Metab 2018; 32 (06) 861-875
• 32 Marcocci C, Cetani F. Clinical practice. Primary hyperparathyroidism. N Engl J Med 2011; 365 (25) 2389-2397 Published correction appears in N Engl J Med 2012;366(22):2138
• 33 Pitt MJ. Rickets and osteomalacia are still around. Radiol Clin North Am 1991; 29 (01) 97-118
• 34 Berry JL, Davies M, Mee AP. Vitamin D metabolism, rickets, and osteomalacia. Semin Musculoskelet Radiol 2002; 6 (03) 173-182
• 35 Tiosano D, Hochberg Z. Hypophosphatemia: the common denominator of all rickets. J Bone Miner Metab 2009; 27 (04) 392-401
• 36 Allgrove J, Shaw NJ. A practical approach to vitamin D deficiency and rickets. Endocr Dev 2015; 28: 119-133
• 37 Mughal MZ, Salama H, Greenaway T, Laing I, Mawer EB. Lesson of the week: florid rickets associated with prolonged breast feeding without vitamin D supplementation. BMJ 1999; 318 (7175): 39-40
• 38 Whyte MP. Hypophosphatasia—aetiology, nosology, pathogenesis, diagnosis and treatment. Nat Rev Endocrinol 2016; 12 (04) 233-246
• 39 Mornet E. Hypophosphatasia. Metabolism 2018; 82: 142-155
• 40 Bangura A, Wright L, Shuler T. Hypophosphatasia: current literature for pathophysiology, clinical manifestations, diagnosis, and treatment. Cureus 2020; 12 (06) e8594
• 41 Resnick D. The sclerotic vertebral body. JAMA 1983; 249 (13) 1761-1763
• 42 Tejwani NC, Schachter AK, Immerman I, Achan P. Renal osteodystrophy. J Am Acad Orthop Surg 2006; 14 (05) 303-311
• 43 Goodman WC, Coburn JW, Slatopolsky E, Salusky IB, Quarles LD. Renal osteodystrophy in adults and children. In: Favus M. ed. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 3th ed.. Washington, DC: American Society for Bone and Mineral Research; 2003: 341-360
• 44 Kemper MJ, van Husen M. Renal osteodystrophy in children: pathogenesis, diagnosis and treatment. Curr Opin Pediatr 2014; 26 (02) 180-186
• 45 Moorthi RN, Moe SM. Recent advances in the noninvasive diagnosis of renal osteodystrophy. Kidney Int 2013; 84 (05) 886-894
• 46 Torres A, Lorenzo V, Gonzalez-Posada JM. Comparison of histomorphometry and computerized tomography of the spine in quantitating trabecular bone in renal osteodystrophy. Nephron 1986; 44 (04) 282-287
• 47 Lima EM, Goodman WG, Kuizon BD. et al. Bone density measurements in pediatric patients with renal osteodystrophy. Pediatr Nephrol 2003; 18 (06) 554-559
• 48 Denburg MR, Tsampalieros AK, de Boer IH. et al. Mineral metabolism and cortical volumetric bone mineral density in childhood chronic kidney disease. J Clin Endocrinol Metab 2013; 98 (05) 1930-1938
• 49 Jamal SA, Gilbert J, Gordon C, Bauer DC. Cortical pQCT measures are associated with fractures in dialysis patients. J Bone Miner Res 2006; 21 (04) 543-548
• 50 Vierucci F, Saggese G, Cimaz R. Osteoporosis in childhood. Curr Opin Rheumatol 2017; 29 (05) 535-546
• 51 Marrani E, Giani T, Simonini G, Cimaz R. Pediatric osteoporosis: diagnosis and treatment considerations. Drugs 2017; 77 (06) 679-695
• 52 Ward LM, Konji VN, Ma J. The management of osteoporosis in children. Osteoporos Int 2016; 27 (07) 2147-2179
• 53 Williams KM. Update on bone health in pediatric chronic disease. Endocrinol Metab Clin North Am 2016; 45 (02) 433-441
• 54 Canalis E, Mazziotti G, Giustina A, Bilezikian JP. Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int 2007; 18 (10) 1319-1328
• 55 Gordon CM, Leonard MB, Zemel BS. International Society for Clinical Densitometry. 2013 Pediatric Position Development Conference: executive summary and reflections. J Clin Densitom 2014; 17 (02) 219-224 . Published correction appears in J Clin Densitom 2014;17(4):517
• 56 Bachrach LK, Gordon CM. SECTION ON ENDOCRINOLOGY. Bone densitometry in children and adolescents. Pediatrics 2016; 138 (04) e20162398
• 57 Genant HK, Wu CY, van Kuijk C, Nevitt MC. Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 1993; 8 (09) 1137-1148
• 58 Bacon S, Crowley R. Developments in rare bone diseases and mineral disorders. Ther Adv Chronic Dis 2018; 9 (01) 51-60
• 59 Stoker DJ. Osteopetrosis. Semin Musculoskelet Radiol 2002; 6 (04) 299-305
• 60 Stark Z, Savarirayan R. Osteopetrosis. Orphanet J Rare Dis 2009; 4: 5