#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#
preLekára.sk / Odborné časopisy / Clinical Osteology / 2020 - 4

Diagnosis and treatment of Paget´s disease of bone: update 2020

Česká verzia

Authors: Zikán Vít
Authors place of work: Osteocentrum, III. interní klinika 1. LF UK a VFN v Praze
Published in the journal: Clinical Osteology 2020; 25(4): 189-200
Category: Doporučené postupy

Summary

Paget’s disease of bone is a progressive focal disorder of bone metabolism characterized by an accelerated rate of bone remodeling, resulting in overgrowth of bone at selected sites and impaired integrity of affected bone. The risk of developing Paget’s disease increases with age and its onset is typically after age 55. Both genetic and environmental causes are thought to contribute to its pathogenesis. The main clinical manifestations are pain, deformities and secondary consequences of bone overgrowth in affected areas, such as osteoarthritis or nerve impingement, although many patients are asymptomatic. Radionuclide bone scan, in addition to targeted radiographs, are recommended as a means of fully and accurately defining the extent of metabolically active disease. In most patients, the serum alkaline phosphatase is elevated. Patients with Paget’s disease who are symptomatic or at risk of complications should be treated with aminobisphosphonates. Zoledronic acid is recommended as first-line therapy producing sustained remissions in almost all patients.

Keywords:

diagnosis – Paget’s disease of bone –treatment – zoledronic acid

Zdroje
  1. Paget J. On a form of chronic inflammation of bones (osteitis deformans). Med Chir Trans 1877; 60: 37–64.9. Dostupné z DOI: <http://dx.doi.org/10.1177/095952877706000105>.
  2. van Staa TP, Selby P, Leufkens HG et al. Incidence and natural history of Paget’s disease of bone in England and Wales. J Bone Miner Res 2002; 17(3): 465–471. Dostupné z DOI: <http://dx.doi.org/10.1359/jbmr.2002.17.3.465>.
  3. Corral‐Gudino L, Borao‐Cengotita‐Bengoa M, Del Pino‐Montes J et al. Epidemiology of Paget’s disease of bone: a systematic review and meta‐analysis of secular changes. Bone 2013; 55(2): 347–352. Dostupné z DOI: <http://dx.doi.org/10.1016/j.bone.2013.04.024>.
  4. Altman RD, Bloch DA, Hochberg MC et al. Prevalence of pelvic Paget’s disease of bone in the United States. J Bone Miner Res 2000; 15(3): 461–465. Dostupné z DOI: <http://dx.doi.org/10.1359/jbmr.2000.15.3.461>.
  5. Yip KM, Lee YL, Kumta SM et al. The second case of Paget’s disease (osteitis deformans) in a Chinese lady. Singapore Med J 1996; 37(6): 665–667.
  6. Siris ES, Ottman R, Flaster E et al. Familial aggregation of Paget’s disease of bone. J Bone Miner Res 1991; 6(5): 495–500. Dostupné z DOI: <http://dx.doi.org/10.1002/jbmr.5650060511>.
  7. Cooper C, Dennison E, Schafheutle K et al. Epidemiology of Paget’s disease of bone. Bone 1999; 24(5 Suppl): 3S-5S. Dostupné z DOI: <http://dx.doi.org/10.1016/s8756–3282(99)00023-x>.
  8. Rendina D, Gennari L, De Filippo G et al. Evidence for increased clinical severity of familial and sporadic Paget’s disease of bone in Campania, southern Italy. J Bone Miner Res 2006; 21(12): 1828–1835. Dostupné z DOI: <http://dx.doi.org/10.1359/jbmr.060822>.
  9. Morales-Piga AA, Bachiller-Corral FJ, Abraira V et al. Is clinical expressiveness of Paget’s disease of bone decreasing? Bone 2002; 30(2): 399–403. Dostupné z DOI: <http://dx.doi.org/10.1016/s8756–3282(01)00674–3>.
  10. Doyle T, Gunn J, Anderson G et al. Paget’s disease in New Zealand: evidence for declining prevalence. Bone 2002; 31(5): 616–619. Dostupné z DOI: <http://dx.doi.org/10.1016/s8756–3282(02)00876–1>.
  11. Tiegs RD, Lohse CM, Wollan PC et al. Long-term trends in the incidence of Paget’s disease of bone. Bone 2000; 27(3): 423–427. Dostupné z DOI: <http://dx.doi.org/10.1016/s8756–3282(00)00333–1>.
  12. Cundy T, Reid IR. Paget’s disease of bone. Clin Biochem 2012; 45(1–2): 43–48. Dostupné z DOI: <http://dx.doi.org/10.1016/j.clinbiochem.2011.09.026>.
  13. Siris ES, Ottman R, Flaster E et al. Familial aggregation of Paget’s disease of bone. J Bone Miner Res 1991; 6(5): 495–500. Dostupné z DOI: <http://dx.doi.org/10.1002/jbmr.5650060511>.
  14. Seton M, Choi HK, Hansen MF et al. Analysis of environmental factors in familial versus sporadic Paget’s disease of bone – the New England Registry for Paget’s Disease of Bone. J Bone Miner Res 2003; 18(8): 1519–1524. Dostupné z DOI: <http://dx.doi.org/10.1359/jbmr.2003.18.8.1519>.
  15. Merlotti D, Gennari L, Galli B et al. Characteristics and familial aggregation of Paget’s disease of bone in Italy. J Bone Miner Res 2005; 20(8): 1356–1364. Dostupné z DOI: <http://dx.doi.org/10.1359/JBMR.050322>.
  16. Morales-Piga AA, Rey-Rey JS, Corres-González J et al. Frequency and characteristics of familial aggregation of Paget’s disease of bone. J Bone Miner Res 1995; 10(4): 663–670. Dostupné z DOI: <http://dx.doi.org/10.1002/jbmr.5650100421>.
  17. Alonso N, Calero-Paniagua I, Del Pino-Montes J. Clinical and Genetic Advances in Paget’s Disease of Bone: a Review. Clin Rev Bone Miner Metab 2017; 15(1): 37–48. Dostupné z DOI: <http://dx.doi.org/10.1007/s12018–016–9226–0>.
  18. Chung PY, Beyens G, Boonen S et al. The majority of the genetic risk for Paget’s disease of bone is explained by genetic variants close to the CSF1, OPTN, TM7SF4, and TNFRSF11A genes. Hum Genet 2010; 128(6): 615–626. Dostupné z DOI: <http://dx.doi.org/10.1007/s00439–010–0888–2>.
  19. Albagha OM, Visconti MR, Alonso N et al. Genome-wide association study identifies variants at CSF1, OPTN and TNFRSF11A as genetic risk factors for Paget’s disease of bone. Nat Genet 2010; 42(6): 520–524. Dostupné z DOI: <http://dx.doi.org/10.1038/ng.562>.
  20. Albagha OM, Wani SE, Visconti MR et al. Genome-wide association identifies three new susceptibility loci for Paget’s disease of bone. Nat Genet 2011; 43(7): 685–689. Dostupné z DOI: <http://dx.doi.org/10.1038/ng.845>.
  21. Beauregard M, Gagnon E, Guay-Bélanger S et al. Identification of rare genetic variants in novel loci associated with Paget’s disease of bone. Hum Genet 2014; 133(6): 755–768. Dostupné z DOI: <http://dx.doi.org/10.1007/s00439–013–1409-x>.
  22. Usategui-Martín R, García-Aparicio J, Corral-Gudino L et al. Polymorphisms in autophagy genes are associated with paget disease of bone. PLoS One 2015; 10(6): e0128984. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pone.0128984>.
  23. Laurin N, Brown JP, Morissette J et al. Recurrent mutation of the gene encoding sequestosome 1 (SQSTM1/p62) in Paget disease of bone. Am J Hum Genet 2002; 70(6):1582–1588. Dostupné z DOI: <http://dx.doi.org/10.1086/340731>.
  24. Morissette J, Laurin N, Brown JP. Sequestosome 1: mutation frequencies, haplotypes, and phenotypes in familial Paget’s disease of bone. J Bone Miner Res 2006; 21(Suppl 2): P38-P44. Dostupné z DOI: <http://dx.doi.org/10.1359/jbmr.06s207>.
  25. Rea SL, Walsh JP, Ward L et al. A novel mutation (K378X) in the sequestosome 1 gene associated with increased NF-kappaB signaling and Paget’s disease of bone with a severe phenotype. J Bone Miner Res 2006; 21(7): 1136–1145. Dostupné z DOI: <http://dx.doi.org/10.1359/jbmr.060405>.
  26. Cundy T, Rutland MD, Naot D et al. Evolution of Paget’s disease of bone in adults inheriting SQSTM1 mutations. Clin Endocrinol (Oxf) 2015; 83(3): 315–319. Dostupné z DOI: <http://dx.doi.org/10.1111/cen.12741>.
  27. Goode A, Long JE, Shaw B et al. Paget disease of bone-associated UBA domain mutations of SQSTM1 exert distinct effects on protein structure and function. Biochim Biophys Acta 2014; 1842(7): 992–1000. Dostupné z DOI: <http://dx.doi.org/10.1016/j.bbadis.2014.03.006>.
  28. Hiruma Y, Kurihara N, Subler MA et al. A SQSTM1/p62 mutation linked to Paget’s disease increases the osteoclastogenic potential of the bone microenvironment. Hum Mol Genet 2008; 17(23): 3708–3719. Dostupné z DOI: <http://dx.doi.org/10.1093/hmg/ddn266>.
  29. Kurihara N, Hiruma Y, Zhou H et al. Mutation of the sequestosome 1 (p62) gene increases osteoclastogenesis but does not induce Paget disease. J Clin Invest 2007; 117(1):133–142. Dostupné z DOI: <http://dx.doi.org/10.1172/JCI28267>.
  30. Reddy SV, Kurihara N, Menaa C et al. Osteoclasts formed by measles virus-infected osteoclast precursors from hCD46 transgenic mice express characteristics of pagetic osteoclasts. Endocrinology 2001; 142(7): 2898–2905. Dostupné z DOI: <http://dx.doi.org/10.1210/endo.142.7.8255>.
  31. Kurihara N, Reddy SV, Menaa C et al. Osteoclasts expressing the measles virus nucleocapsid gene display a pagetic phenotype. J Clin Invest 2000; 105(5):607–614. Dostupné z DOI: <http://dx.doi.org/10.1172/JCI8489>.
  32. Kurihara N, Hiruma Y, Yamana K et al. Contributions of the measles virus nucleocapsid gene and the SQSTM1/p62(P392L) mutation to Paget’s disease. Cell Metab 2011; 13(1): 23–34. Dostupné z DOI: <http://dx.doi.org/10.1016/j.cmet.2010.12.002>.
  33. Teramachi J, Nagata Y, Mohammad K et al. Measles virus nucleocapsid protein increases osteoblast differentiation in Paget’s disease. J Clin Invest 2016; 126(3): 1012–1022. Dostupné z DOI: <http://dx.doi.org/10.1172/JCI82012>.
  34. Mills BG, Singer FR, Weiner LP et al. Cell cultures from bone affected by Paget’s disease. Arthritis Rheum 1980; 23(10): 1115–1120. Dostupné z DOI: <http://dx.doi.org/10.1002/art.1780231007>.
  35. Rebel A, Basle M, Pouplard A et al. Towards a viral etiology for Paget’s disease of bone. Metab Bone Dis Relat Res 1981; 3(4–5): 235–238. Dostupné z DOI: <http://dx.doi.org/10.1016/0221–8747(81)90038–2>.
  36. Singer FR. Paget’s disease of bone-genetic and environmental factors. Nat Rev Endocrinol 2015; 11(11): 662–671. Dostupné z DOI: <http://dx.doi.org/10.1038/nrendo.2015.138>
  37. Devogelaer JP, Bergmann P, Body JJ et al. Management of patients with Paget’s disease: a consensus document of the Belgian Bone Club. Osteoporos Int 2008; 19(8): 1109–1017. Dostupné z DOI: <http://dx.doi.org/10.1007/s00198–008–0629–8>.
  38. Siris E, Roodman GD. Paget Disease Section X. In: Favus MJ (ed). Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. ASBMR: Washington (DC) 2003. ISBN 978–0974478203.
  39. Dabbs TR, Skjodt K. Prevalence of angioid streaks and other ocular complications of Paget’s disease of bone. Br J Ophthalmol 1990; 74(10): 579–582. Dostupné z DOI: <http://dx.doi.org/10.1136/bjo.74.10.579>.
  40. Yost JH, Spencer-Green G, Krant JD. Vascular steal mimicking compression myelopathy in Paget’s disease of bone: rapid reversal with calcitonin and systemic steroids. J Rheumatol 1993; 20(6): 1064–1065.
  41. Whyte MP. Clinical practice. Paget’s disease of bone. N Engl J Med 2006; 355(6): 593–600. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMcp060278>.
  42. Redden JF, Dixon J, Vennart W et al. Management of fissure fractures in Paget’s disease. Int Orthop 1981; 5(2): 103–106. Dostupné z DOI: <http://dx.doi.org/10.1007/BF00267839>.
  43. Wermers RA, Tiegs RD, Atkinson EJ et al. Morbidity and mortality associated with Paget’s disease of bone: a population-based study. J Bone Miner Res. 2008; 23(6): 819–825. Dostupné z DOI: <http://dx.doi.org/10.1359/jbmr.080215>.
  44. Hansen MF, Seton M, Merchant A. Osteosarcoma in Paget’s disease of bone. J Bone Miner Res 2006; Suppl 2: P58-P63. Dostupné z DOI: <http://dx.doi.org/10.1359/jbmr.06s211>.
  45. Ralston SH, Langston AL, Reid IR. Pathogenesis and management of Paget’s disease of bone. Lancet 2008; 372(9633): 155–163. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(08)61035–1>.
  46. Rendina D, Mossetti G, Soscia E et al. Giant cell tumor and Paget’s disease of bone in one family: geographic clustering. Clin Orthop Relat Res 2004; (421): 218–224. Dostupné z DOI: <http://dx.doi.org/10.1097/00000118702.46373.e3>.
  47. Rendina D, De Filippo G, Ralston SH et al. Clinical characteristics and evolution of giant cell tumor occurring in Paget’s disease of bone. J Bone Miner Res 2015; 30(2): 257–263. Dostupné z DOI: <http://dx.doi.org/10.1002/jbmr.2349>.
  48. Alvarez L, Guañabens N, Peris P et al. Usefulness of biochemical markers of bone turnover in assessing response to the treatment of Paget’s disease. Bone 2001; 29(5): 447–452. Dostupné z DOI: <http://dx.doi.org/10.1016/s8756–3282(01)00592–0>.
  49. Reid IR, Davidson JS, Wattie D et al. Comparative responses of bone turnover markers to bisphosphonate therapy in Paget’s disease of bone. Bone 2004; 35(1): 224–230. Dostupné z DOI: <http://dx.doi.org/10.1016/j.bone.2004.03.023>.
  50. Peris P, Alvarez L, Vidal S et al. Biochemical response to bisphosphonate therapy in pagetic patients with skull involvement. Calcif Tissue Int 2006; 79(1):22–26. Dostupné z DOI: <http://dx.doi.org/10.1007/s00223–005–0247–9>.
  51. Shankar S, Hosking DJ. Biochemical assessment of Paget’s disease of bone. J Bone Miner Res 2006; 21(Suppl 2): P22-P27. Dostupné z DOI: <http://dx.doi.org/10.1359/jbmr.06s204>.
  52. Seton M. Paget’s disease of bone. In: Hochberg MC, Silman AJ, Smolen JS et al (eds). Rheumatology. 4th ed. Mosby (Elsevier): Philadelphia 2007. ISBN 978–0323044301.
  53. Griffiths HJ. Radiology of Paget’s disease. Curr Opin Radiol 1992; 4(6):124–128.
  54. Singer FR, Bone HG, Hosking DJ et al. Paget’s disease of bone: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2014; 99(12): 4408–4422. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2014–2910>.
  55. Ralston SH, Corral-Gudino L, Cooper C et al. Diagnosis and Management of Paget’s Disease of Bone in Adults: A Clinical Guideline. J Bone Miner Res 2019; 34(4): 579–604. Dostupné z DOI: <http://dx.doi.org/10.1002/jbmr.3657>.
  56. Whyte MP. Clinical practice. Paget’s disease of bone. N Engl J Med 2006; 355(6): 593–600. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMcp060278>.
  57. Sundaram M, Khanna G, El-Khoury GY. T1-weighted MR imaging for distinguishing large osteolysis of Paget’s disease from sarcomatous degeneration. Skeletal Radiol 2001; 30(7): 378–383. Dostupné z DOI: <http://dx.doi.org/10.1007/s002560100360>.
  58. Sundaram M. Imaging of Paget’s disease and fibrous dysplasia of bone. J Bone Miner Res 2006; 21(Suppl 2): P28-P30. Dostupné z DOI: <http://dx.doi.org/10.1359/jbmr.06s205>
  59. Spieth ME, Kasner DL, Manor WF. Positron emission tomography and Paget disease: hot is not necessarily malignant. Clin Nucl Med 2003; 28(9): 773–774. Dostupné z DOI: <http://dx.doi.org/10.1097/01.rlu.0000082671.73091.db>.
  60. Singer FR, Bone HG 3rd, Hosking DJ et al. Paget’s disease of bone: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2014; 99(12): 4408–4422. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2014–2910>.
  61. Reid IR, Nicholson GC, Weinstein RS et al. Biochemical and radiologic improvement in Paget’s disease of bone treated with alendronate: a randomized, placebo-controlled trial. Am J Med 1996; 101(4): 341–348. Dostupné z DOI: <http://dx.doi.org/10.1016/s0002–9343(96)00227–6>.
  62. Siris E, Weinstein RS, Altman R et al. Comparative study of alendronate versus etidronate for the treatment of Paget’s disease of bone. J Clin Endocrinol Metab 1996; 81(3): 961–967. Dostupné z DOI: <http://dx.doi.org/10.1210/jcem.81.3.8772558>.
  63. Walsh JP, Ward LC, Stewart GO et al. A randomized clinical trial comparing oral alendronate and intravenous pamidronate for the treatment of Paget’s disease of bone. Bone 2004; 34(4): 747–754. Dostupné z DOI: <http://dx.doi.org/10.1016/j.bone.2003.12.011>.
  64. Brown JP, Chines AA, Myers WR et al. Improvement of pagetic bone lesions with risedronate treatment: a radiologic study. Bone 2000; 26(3): 263–267. Dostupné z DOI: <http://dx.doi.org/10.1016/s8756–3282(99)00271–9>.
  65. Ralston SH, Corral-Gudino L, Cooper C et al. Diagnosis and management of Paget’s disease of bone in adults: a clinical guideline. J Bone Miner Res 2019; 34(4): 579–604. Dostupné z DOI: <http://dx.doi.org/10.1002/jbmr.3657>.
  66. Reid IR, Miller P, Lyles K et al. Comparison of a single infusion of zoledronic acid with risedronate for Paget’s disease. N Engl J Med 2005; 353(9): 898–908. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa044241>.
  67. Reid IR, Lyles K, Su G et al. A single infusion of zoledronic acid produces sustained remissions in Paget disease: data to 6.5 years. J Bone Miner Res 2011; 26(9): 2261–2270. Dostupné z DOI: <http://dx.doi.org/10.1002/jbmr.438>.
  68. Cundy T, Maslowski K, Grey A et al. Durability of Response to Zoledronate Treatment and Competing Mortality in Paget’s Disease of Bone. J Bone Miner Res 2017; 32(4):753–756. Dostupné z DOI: <http://dx.doi.org/10.1002/jbmr.3029>
  69. Merlotti D, Gennari L, Martini G et al. Comparison of different intravenous bisphosphonate regimens for Paget’s disease of bone. J Bone Miner Res 2007; 22(10): 1510–1517. Dostupné z DOI: <http://dx.doi.org/10.1359/jbmr.070704>.
  70. Hosking D, Lyles K, Brown JP et al. Long-term control of bone turnover in Paget’s disease with zoledronic acid and risedronate. J Bone Miner Res 2007; 22(1): 142–148. Dostupné z DOI: <http://dx.doi.org/10.1359/jbmr.061001.22:142>.
  71. Miller PD, Roux C, Boonen S et al. Safety and efficacy of risedronate in patients with age-related reduced renal function as estimated by the Cockcroft and Gault method: a pooled analysis of nine clinical trials. J Bone Miner Res 2005; 20(12): 2105–2115. Dostupné z DOI: <http://dx.doi.org/10.1359/JBMR.050817>.
  72. Jamal SA, Bauer DC, Ensrud KE et al. Alendronate treatment in women with normal to severely impaired renal function: an analysis of the fracture intervention trial. J Bone Miner Res 2007; 22(4): 503–508. Dostupné z DOI: <http://dx.doi.org/10.1359/jbmr.070112>.
  73. Miller PD. The kidney and bisphosphonates. Bone 2011; 49(1): 77–81. Dostupné z DOI: <http://dx.doi.org/10.1016/j.bone.2010.12.024>.
  74. Reid IR, Sharma S, Kalluru R et al. Treatment of Paget’s Disease of Bone with Denosumab: Case Report and Literature Review. Calcif Tissue Int 2016; 99(3): 322–325. Dostupné z DOI: <http://dx.doi.org/10.1007/s00223–016–0150–6>.
  75. Huynh AL, Baker ST, Stewardson AJ et al. Denosumab-associated hypocalcaemia: incidence, severity and patient characteristics in a tertiary hospital setting. Pharmacoepidemiol Drug Saf 2016; 25(11): 1274–1278. Dostupné z DOI: <http://dx.doi.org/10.1002/pds.4045>.
  76. Jalleh R, Basu G, Le Leu R et al. Denosumab-Induced Severe Hypocalcaemia in Chronic Kidney Disease. Case Rep Nephrol 2018; 2018: 7384763. Dostupné z DOI: <http://dx.doi.org/10.1155/2018/7384763>.
  77. Parvizi J, Schall DM, Lewallen DG et al. Outcome of uncemented hip arthroplasty components in patients with Paget’s disease. Clin Orthop Relat Res 2002; (403): 127–134. Dostupné z DOI: <http://dx.doi.org/10.1097/00003086–200210000–00020>.
  78. Hernandez NM, Vakharia RM, Mont MA et al. Paget’s disease in primary total hip arthroplasty is associated with greater in-hospital lengths of stay, costs, and complications. J Arthroplasty 2020; S0883–5403(20)30896–2. Dostupné z DOI: <http://dx.doi.org/10.1016/j.arth.2020.08.017>.
  79. Kaplan FS. Surgical management of Paget’s disease. J Bone Miner Res 1999; 14(Suppl 2): 34–38. Dostupné z DOI: <http://dx.doi.org/10.1002/jbmr.5650140208>.
  80. Wegrzyn J, Pibarot V, Chapurlat R et al. Cementless total hip arthroplasty in Paget’s disease of bone: a retrospective review. Int Orthop 2010; 34(8): 1103–1109. Dostupné z DOI: <http://dx.doi.org/10.1007/s00264–009–0853–7>.
  81. Whitson HE, Lobaugh B, Lyles KW. Severe hypocalcemia following bisphosphonate treatment in a patient with Paget’s disease of bone. Bone 2006; 39(4): 954–958. Dostupné z DOI: <http://dx.doi.org/10.1016/j.bone.2006.04.032>.
  82. Alvarez L, Peris P, Guañabens N et al. Long-term biochemical response after bisphosphonate therapy in Paget’s disease of bone. Proposed intervals for monitoring treatment. Rheumatology (Oxford) 2004; 43(7): 869–874. Dostupné z DOI: <http://dx.doi.org/10.1093/rheumatology/keh185>.
  83. Reid IR, Maslowski K. Long-Term Bone Scintigraphy Results After Intravenous Zoledronate in Paget’s Disease of Bone. Calcif Tissue Int 2017; 101(1): 43–49. Dostupné z DOI: <http://dx.doi.org/10.1007/s00223–017–0261–8>.
  84. Siris ES, Feldman F. Natural history of untreated Paget’s disease of the tibia. J Bone Miner Res 1997; 12(4): 691–692. Dostupné z DOI: <http://dx.doi.org/10.1359/jbmr.1997.12.4.691>.
Štítky
Biochémia Detská gynekológia Detská rádiológia Detská reumatológia Endokrinológia Gynekológia a pôrodníctvo Interné lekárstvo Ortopédia Praktické lekárstvo pre dospelých Rádiodiagnostika Rehabilitácia Reumatológia Traumatológia Osteologie
Článek Mnohostranné dopady pandemie
Článek Může být FRAX přínosnější? Editorial
Článek Adjusting conventional FRAX estimates of fracture probability according to the recency of sentinel fractures
Článek Kost a imunitní systém – osteoimunologie
Článek Vitamín D a kvalita kosti
Článek Nutriční (vitamin D deficitní) rachitis – opomíjená diagnóza? Kazuistika
Článok vyšiel v časopise

Clinical Osteology

Číslo 4
2020 Číslo 4
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.
Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#