New insights into the pathophysiology and management of osteoporosis in patients with beta thalassaemia

British Journal of Haematology

Volumn 127, Issue 2, 2004, Pages 127-139

  Voskaridou, Ersi ^a   Terpos, Evangelos ^b,c  

^a LAIKO GENERAL HOSPITAL   (Greece)

^b General Airforce Hospital   (Greece)

^c HAMMERSMITH HOSPITAL   (United Kingdom)

Author keywords

Beta thalassaemia; Bisphosphonates; Osteoporosis; Osteoprotegerin; Receptor activator of nuclear factor kappa B ligand

Indexed keywords

ALENDRONIC ACID; BISPHOSPHONIC ACID DERIVATIVE; CALCITONIN; CALCIUM; CHORIONIC GONADOTROPIN; CLODRONIC ACID; COLECALCIFEROL; COLLAGEN TYPE 1; ESTROGEN; HYDROXYUREA; OSTEOCLAST DIFFERENTIATION FACTOR; OSTEOPROTEGERIN; PAMIDRONIC ACID; VITAMIN D;

BETA THALASSEMIA; BONE INJURY; BONE MARROW; BONE MASS; CELL ACTIVATION; CELL PROLIFERATION; DRUG POTENCY; ENDOCRINE DISEASE; FEMALE; GENETIC POLYMORPHISM; HUMAN; IRON OVERLOAD; MALE; MORBIDITY; OSTEOBLAST; OSTEOCLAST; OSTEOLYSIS; OSTEOPOROSIS; PATHOGENESIS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; SYSTEMATIC REVIEW; THALASSEMIA MAJOR; TREATMENT OUTCOME;

ADULT; BETA-THALASSEMIA; COLLAGEN TYPE I; DIPHOSPHONATES; HORMONE REPLACEMENT THERAPY; HUMANS; OSTEOBLASTS; OSTEOCLASTS; OSTEOPOROSIS; POLYMORPHISM, GENETIC;

EID: 5644257032     PISSN: 00071048     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1365-2141.2004.05143.x     Document Type: Review

References (114)

1. Abdollah Shamshirsaz, A., Bekheirnia, M.R., Kamgar, M., Pourzahedgilani, N., Bouzari, N., Habibzadeh, M., Hashemi, R., Abdollah Shamshirsaz, A.H., Aghakhani, S., Homayoun, H. & Larijani, B. (2003) Metabolic and endocrinologic complications in beta-thalassemia major: a multicenter study in Tehran. BMC Endocrine Disorders, 3, 1-6.
2. Abe, E., Yamamoto, M., Taguchi, Y., Lecka-Czernik, B., O'Brien, C.A., Economides, A.N., Stahl, N., Jilka, R.L. & Manolagas, S.C. (2000) Essential requirement of BMPs-2/4 for both osteoblast and osteoclast formation in murine bone marrow cultures from adult mice: antagonism by noggin. Journal of Bone and Mineral Research, 15, 663-673.
3. Ahdjoudj, S., Fromigue, O. & Marie, P.J. (2004) Plasticity and regulation of human bone marrow stromal osteoprogenitor cells: potential implication in the treatment of age-related bone loss. Histology and Histopathology, 19, 151-157.
4. Anapliotou, M.L., Kastanias, I.T., Psara, P., Evangelou, E.A., Liparaki, M. & Dimitriou, P. (1995) The contribution of hypogonadism to the development of osteoporosis in thalassaemia major: new therapeutic approaches. Clinical Endocrinology, 42, 279-287.
5. Angastiniotis, M., Pavlides, N., Aristidou, K., Kanakas, A., Yerakaris, M., Eracleous, E. & Posporis, T. (1998) Bone pain in thalassaemia: assessment of DEXA and MRI findings. Journal of Pediatric Endocrinology and Metabolism, 11 (Suppl. 3), 779-784.
6. Arcasoy, A., Canata, D., Sinav, B., Kutlay, L., Oguz, N. & Sen, M. (2001) Serum zinc levels and zinc binding capacity in thalassemia. Journal of Trace Elements in Medicine and Biology, 15, 85-87.
7. Bekheirnia, M.R., Abllah Shahirsaz, A., Kamgar, M., Bouzari, N., Erfanzadeh, G., Pourzahedgilani, N., Tataie, S.M., Abllah Shahirsaz, A., Kimiagar, M., Ezzati, F. & Larijani, B. (2004) Serum zinc and its relation to bone mineral density in beta-thalassemic adolescents. Biological Trace Element Research, 97, 215-224.
8. Berkovitch, M., Bistritzer, T., Milone, S.D., Perlman, K., Kucharczyk, W. & Olivieri, N.F. (2000) Iron deposition in the anterior pituitary in homozygous beta-thalassemia: MRI evaluation and correlation with gonadal function. Journal of Pediatric Endocrinology and Metabolism, 13, 179-184.
9. Bertoldo, F., D'Agruma, L., Furlan, F., Colapietro, F., Lorenzi, M.T., Maiorano, N., Iolascon, A., Zelante, L., Locascio, V. & Gasparini, P. (2000) Transforming growth factor-beta1 gene polymorphism, bone turnover, and bone mass in Italian postmenopausal women. Journal of Bone and Mineral Research, 15, 634-639.
10. Binkley, N.C., Schmeer, P., Wasnich, R.D. & Lenchik, L. (2002) What are the criteria by which a densitometric diagnosis of osteoporosis can be made in males and non-Caucasians? Journal of Clinical Densitometry, 5(Suppl.), 19-27.
11. Body, J.J. (1998) Bisphosphonates. European Journal of Cancer, 34, 263-269.
12. Body, J.J., Greipp, P., Coleman, R.E., Facon, T., Geurs, F., Fermand, J.P., Harousseau, J.L., Lipton, A., Mariette, X., Williams, C.D., Nakanishi, A., Holloway, D., Martin, S.W., Dunstan, C.R. & Bekker, P.J. (2003) A phase I study of AMGN-0007, a recombinant osteoprotegerin construct, in patients with multiple myeloma or breast carcinoma related bone metastases. Cancer, 97 (3 Suppl.), 887-892.
13. Bonjour, J.P., Ammann, P. & Rizzoli, R. (1999) Importance of preclinical studies in the development of drugs for treatment of osteoporosis: a review related to the 1998 WHO guidelines. Osteoporosis International, 9, 379-393.
14. Brill, P.W., Winchester, P., Giardina, P.J. & Cunningham-Rundles, S. (1991) Deferoxamine-induced bone dysplasia in patients with thalassemia major. American Journal of Roentgenology, 156, 561-565.
15. Bucay, N., Sarosi, I., Dunstan, C.R., Morony, S., Tarpley, J., Capparelli, C., Scully, S., Tan, H.L., Xu, W., Lacey, D.L., Boyle, W.J. & Simonet, W.S. (1998) Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes & Development, 12, 1260-1268.
16. Byers, P.H. & Steiner, R.D. (1992) Osteogenesis imperfecta. Annual Review of Medicine, 43, 269-282.
17. Canatan, D., Akar, N. & Arcasoy, A. (1995) Effects of calcitonin therapy on osteoporosis in patients with thalassemia. Acta Haematologica, 93, 20-24.
18. Carmina, E., Di Fede, G., Napoli, N., Renda, G., Vitale, G., Lo Pinto, C., Bruno, D., Malizia, R. & Rini, G.B. (2004) Hypogonadism and hormone replacement therapy on bone mass of adult women with thalassemia major. Calcified Tissue International, 74, 68-71.
19. Cefalu, C.A. (2004) Is bone mineral density predictive of fracture risk reduction? Current Medical Research and Opinion, 20, 341-349.
20. Chan, Y.L., Pang, L.M., Chik, K.W., Cheng, J.C. & Li, C.K. (2002) Patterns of bone diseases in transfusion-dependent homozygous thalassaemia major: predominance of osteoporosis and desferrioxamine-induced bone dysplasia. Pediatric Radiology, 32, 492-497.
21. Chaudhary, L.R., Hofmeister, A.M. & Hruska, K.A. (2004) Differential growth factor control of bone formation through osteoprogenitor differentiation. Bone, 34, 402-411.
22. Christenson, R.H. (1997) Biochemical markers of bone metabolism: an overview. Clinical Biochemistry, 30, 573-593.
23. Cohen, A.J. & Roe, F.J. (2000) Review of risk factors for osteoporosis with particular reference to a possible aetiological role of dietary salt. Food and Chemical Toxicology, 38, 237-253.
24. Cooley, T.B. & Lee, P. (1925) A series of cases of splenomegaly in children with anemia and peculiar bone change. Transactions of the American Pediatric Society, 37, 29.
25. Cooper, G.S. & Umbach, D.M. (1996) Are vitamin D receptor polymorphisms associated with bone mineral density? A meta-analysis. Journal of Bone and Mineral Research, 11, 1841-1849.
26. Cornish, J., Grey, A., Callon, K.E., Naot, D., Hill, B.L., Lin, C.Q., Balchin, L.M. & Reid, I.R. (2004) Shared pathways of osteoblast mitogenesis induced by amylin, adrenomedullin, and IGF-1. Biochemical and Biophysical Research Communications, 318, 240-246.
27. De Sanctis, V., Pinamonti, A., Di Palma, A., Sprocati, M., Atti, G., Gamberini, M.R. & Vullo, C. (1996) Growth and development in thalassaemia major patients with severe bone lesions due to desferrioxamine. European Journal of Pediatrics, 155, 368-372.
28. De Sanctis, V., Stea, S., Savarino, L., Scialpi, V., Traina, G.C., Chiarelli, G.M., Sprocati, M., Govoni, R., Pezzoli, D., Gamberini, R. & Rigolin, F. (1998) Growth hormone secretion and bone histomorphometric study in thalassaemic patients with acquired skeletal dysplasia secondary to desferrioxamine. Journal of Pediatric Endocrinology and Metabolism, 11(Suppl. 3), 827-833.
29. De Vernejoul, M.C., Girot, R., Gueris, J., Cancela, L., Bang, S., Bielakoff, J., Mautalen, C., Goldberg, D. & Miravet, L. (1982) Calcium phosphate metabolism and bone disease in patients with homozygous thalassemia. Journal of Clinical Endocrinology and Metabolism, 54, 276-281.
30. De Virgiliis, S., Congia, M., Turco, M.P., Frau, F., Dessi, C., Argiolu, F., Sorcinelli, R., Sitzia, A. & Cao, A. (1988) Depletion of trace elements and acute ocular toxicity induced by desferrioxamine in patients with thalassaemia. Archives of Disease in Childhood, 63, 250-255.
31. Di Stefano, M., Chiabotto, P., Roggia, C., Garofalo, F., Lala, R., Piga, A. & Isaia, G.C. (2004) Bone mass and metabolism in thalassemic children and adolescents treated with different iron-chelating drugs. Journal of Bone and Mineral Metabolism, 22, 53-57.
32. Diamond, T., Stiel, D. & Posen, S. (1989) Osteoporosis in hemochromatosis: iron excess, gonadal deficiency, or other factors? Annals of Internal Medicine, 110, 430-436.
33. Dresner Pollack, R., Rachmilewitz, E., Blumenfeld, A., Idelson, M. & Goldfarb, A.W. (2000) Bone mineral metabolism in adults with beta-thalassaemia major and intermedia. British Journal of Haematology, 111, 902-907.
34. Ferrara, M., Matarese, S.M., Francese, M., Borrelli, B., Coppola, A., Coppola, L. & Esposito, L. (2002) Effect of VDR polymorphisms on growth and bone mineral density in homozygous beta thalassaemia. British Journal of Haematology, 117, 436-440.
35. Fleisch, H. (1998) Bisphosphonates: mechanisms of action. Endocrinology Reviews, 19, 80-100.
36. Garofalo, F., Piga, A., Lala, R., Chiabotto, S., Di Stefano, M. & Isaia, G.C. (1998) Bone metabolism in thalassemia. Annals of New York Academy of Sciences, 850, 475-478.
37. Geusens, P.P. & Boonen, S. (2002) Osteoporosis and the growth hormone-insulin-like growth factor axis. Hormone Research, 58(Suppl. 3), 49-55.
38. Giardina, P.J., Schneider, R., Lesser, M., Simmons, B., Rodriguez, A., Gertner, J., New, M. & Hilgartner, M.W. (1995) Abnormal bone metabolism in thalassaemia. In: Endocrine Disorders in Thalassaemia (ed. by S. Ando et al.), pp. 39-46. Springer, Berlin.
39. Goldring, S.R. (2003) Inflammatory mediators as essential elements in bone remodeling. Calcified Tissue International, 73, 97-100.
40. Grampp, S., Genant, H.K., Mathur, A., Lang, P., Jergas, M., Takada, M., Gluer, C.C., Lu, Y. & Chavez, M. (1997) Comparisons of noninvasive bone mineral measurements in assessing age-related loss, fracture discrimination, and diagnostic classification. Journal of Bone and Mineral Research, 12, 697-711.
41. Hajjar, R.R. & Kamel, H.K. (2004) Osteoporosis for the home care physician. Part 1: etiology and current diagnostic strategies. Journal of the American Medical Directors Association, 5, 192-196.
42. Han, K.O., Moon, I.G., Kang, Y.S., Chung, H.Y., Min, H.K. & Han, I.K. (1997) Nonassociation of estrogen receptor genotypes with bone mineral density and estrogen responsiveness to hormone replacement therapy in Korean postmenopausal women. Journal of Clinical Endocrinology and Metabolism, 82, 991-995.
43. Hatori, M., Sparkman, J., Teixeira, C.C., Grynpas, M., Nervina, J., Olivieri, N. & Shapiro, I.M. (1995) Effects of deferoxamine on chondrocyte alkaline phosphatase activity: proxidant role of deferoxamine in thalassemia. Calcified Tissue International, 57, 229-236.
44. Hodge, J.M., Kirkland, M.A., Aitken, C.J., Waugh, C.M., Myers, D.E., Lopez, C.M., Adams, B.E. & Nicholson, G.C. (2004) Osteoclastic potential of human CFU-GM: biphasic effect of GM-CSF. Journal of Bone and Mineral Research, 19, 190-199.
45. Horowitz, M.C., Xi, Y., Wilson, K. & Kacena, M.A. (2001) Control of osteoclastogenesis and bone resorption by members of the TNF family of receptors and ligands. Cytokine and Growth Factor Reviews, 12, 9-18.
46. Itoh, K., Udagawa, N., Matsuzaki, K., Takami, M., Amano, H., Shinki, T., Ueno, Y., Takahashi, N. & Suda, T. (2000) Importance of membrane- or matrix-associated forms of M-CSF and RANKL/ODF in osteoclastogenesis supported by SAOS-4/3 cells expressing recombinant PTH/PTHrP receptors. Journal of Bone and Mineral Research, 15, 1766-1775.
47. Jensen, C.E., Tuck, S.M., Old, J., Morris, R.W., Yardumian, A., De Sanctis, V., Hoffbrand, A.V. & Wonke, B. (1997) Incidence of endocrine complications and clinical disease severity related to genotype analysis and iron overload in patients with beta-thalassaemia. European Journal of Haematology, 59, 76-81.
48. Jensen, C.E., Tuck, S.M., Agnew, J.E., Koneru, S., Morris, R.W., Yardumian, A., Prescott, E., Hoffbrand, A.V. & Wonke, B. (1998) High prevalence of low bone mass in thalassaemia major. British Journal of Haematology, 103, 911-915.
49. Jiang, Y., Zhao, J.J., Mitlak, B.H., Wang, O., Genant, H.K. & Eriksen, E.F. (2003) Recombinant human parathyroid hormone (1-34) [teriparatide] improves both cortical and cancellous bone structure. Journal of Bone and Mineral Research, 18, 1932-1941.
50. Johanson, N.A. (1990) Musculoskeletal problems in hemoglobinopathy. The Orthopedic Clinics of North America, 21, 191-198.
51. Johnston, C.C. Jr., Miller, J.Z., Slemenda, C.W., Reister, T.K., Hui, S., Christian, J.C. & Peacock, M. (1992) Calcium supplementation and increases in bone mineral density in children. New England Journal of Medicine, 327, 82-87.
52. Kim, N., Odgren, P.R., Kim, D.K., Marks, S.C. Jr. & Choi, Y. (2000) Diverse roles of the tumor necrosis factor family member TRANCE in skeletal physiology revealed by TRANCE deficiency and partial rescue by a lymphocyte-expressed TRANCE transgene. Proceedings of the National Academy of Sciences of the United States of America, 97, 10905-10910.
53. Kong, Y.Y., Yoshida, H., Sarosi, I., Tan, H.L., Timms, E., Capparelli, C., Morony, S., Oliveira-dos-Santos, A.J., Van, G., Itie, A., Khoo, W., Wakeham, A., Dunstan, C.R., Lacey, D.L., Mak, T.W., Boyle, W.J. & Penninger, J.M. (1999) OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature, 397, 315-323.
54. Kostenuik, P.J., Bolon, B., Morony, S., Daris, M., Geng, Z., Carter, C. & Sheng, J. (2004) Gene therapy with human recombinant osteoprotegerin reverses established osteopenia in ovariectomized mice. Bone, 34, 656-664.
55. Lala, R., Chiabotto, P., Di Stefano, M., Isaia, G.C., Garofalo, F. & Piga, A. (1998) Bone density and metabolism in thalassaemia. Journal of Pediatric Endocrinology and Metabolism, 11 (Suppl. 3), 785-790.
56. Lane, N.E., Bloch, D.A., Jones, H.H., Marshall, W.H. Jr., Wood, P.D. & Fries, J.F. (1986) Long-distance running, bone density, and osteoarthritis. JAMA, 255, 1147-1151.
57. Langdahl, B.L., Knudsen, J.Y., Jensen, H.K., Gregersen, N. & Eriksen, E.F. (1997) A sequence variation: 713-8delC in the transforming growth factor-beta 1 gene has higher prevalence in osteoporotic women than in normal women and is associated with very low bone mass in osteoporotic women and increased bone turnover in both osteoporotic and normal women. Bone, 20, 289-294.
58. Lasco, A., Morabito, N., Gaudio, A., Buemi, M., Wasniewska, M. & Frisina, N. (2001) Effects of hormonal replacement therapy on bone metabolism in young adults with beta-thalassemia major. Osteoporosis International, 12, 570-575.
59. Lasco, A., Morabito, N., Gaudio, A., Crisafulli, A., Meo, A., Denuzzo, G. & Frisina, N. (2002) Osteoporosis and beta-thalassemia major: role of the IGF-I/IGFBP-III axis. Journal of Endocrinology Investigation, 25, 338-344.
60. Lin, J.H. (1996) Bisphosphonates: a review of their pharmacokinetic properties. Bone, 18, 75-85.
61. Lindsay, R. (1993) Prevention and treatment of osteoporosis. Lancet, 341, 801-805.
62. Ma, E.S., Lam, K.K., Chan, A.Y., Ha, S.Y., Au, W.Y. & Chan, L.C. (2003) Transferrin receptor-2 polymorphisms and iron overload in transfusion independent b-thalassemia intermedia. Haematologica, 88, 345-346 [letter].
63. Mahachoklertwattana, P., Chuansumrit, A., Sirisriro, R., Choubtum, L., Sriphrapradang, A. & Rajatanavin, R. (2003a) Bone mineral density, biochemical and hormonal profiles in suboptimally treated children and adolescents with beta-thalassaemia disease. Clinical Endocrinology, 58, 273-279.
64. Mahachoklertwattana, P., Sirikulchayanonta, V., Chuansumrit, A., Karnsombat, P., Choubtum, L., Sriphrapradang, A., Domrongkitchaiporn, S., Sirisriro, R. & Rajatanavin, R. (2003b) Bone histomorphometry in children and adolescents with beta-thalassemia disease: iron-associated focal osteomalacia. Journal of Clinical Endocrinology and Metabolism, 88, 3966-3972.
65. Malloy, P.J., Weisman, Y. & Feldman, D. (1994) Hereditary 1 alpha, 25-dihydroxyvitamin D-resistant rickets resulting from a mutation in the vitamin D receptor deoxyribonucleic acid-binding domain. Journal of Clinical Endocrinology and Metabolism, 78, 313-316.
66. Masi, L., Becherini, L., Colli, E., Gennari, L., Mansani, R., Falchetti, A., Becorpi, A.M., Cepollaro, C., Gonnelli, S., Tanini, A. & Brandi, M.L. (1998) Polymorphisms of the calcitonin receptor gene are associated with bone mineral density in postmenopausal Italian women. Biochemical and Biophysical Research Communications, 248, 190-195.
67. Meghji, S., Morrison, M.S., Henderson, B. & Arnett, T.R. (2001) pH dependence of bone resorption: mouse calvarial osteoclasts are activated by acidosis. American Journal of Physiology. Endocrinology and Metabolism, 280, E112-E119.
68. Meunier, P.J., Delmas, P.D., Eastell, R., McClung, M.R., Papapoulos, S., Rizzoli, R., Seeman, E. & Wasnich RD. (1999) Diagnosis and management of osteoporosis in postmenopausal women: clinical guidelines. International Committee for Osteoporosis Clinical Guidelines. Clinical Therapeutics, 21, 1025-1044.
69. Meunier, P.J., Roux, C., Seeman, E., Ortolani, S., Badurski, J.E., Spector, T.D., Cannata, J., Balogh, A., Lemmel, E.M., Pors-Nielsen, S., Rizzoli, R., Genant, H.K. & Reginster, J.Y. (2004) The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. New England Journal of Medicine, 350, 459-468.
70. Michelson, J. & Cohen, A. (1988) Incidence and treatment of fractures in thalassemia. Journal of Orthopaedic Trauma, 2, 29-32.
71. Morabito, N., Lasco, A., Gaudio, A., Crisafulli, A., Di Pietro, C., Meo, A. & Frisina, N. (2002) Bisphosphonates in the treatment of thalassemia-induced osteoporosis. Osteoporosis International, 13, 644-649.
72. Morabito, N., Gaudio, A., Lasco, A., Atteritano, M., Pizzoleo, M.A., Cincotta, M., La Rosa, M., Guarino, R., Meo, A. & Frisina, N. (2004) Osteoprotegerin and RANKL in the pathogenesis of thalassemia-induced osteoporosis: new pieces of the puzzle. Journal of Bone and Mineral Research, 19, 722-727.
73. Mori, H., Sakai, H., Morihata, H., Kawawaki, J., Amano, H., Yamano, T. & Kuno, M. (2003) Regulatory mechanisms and physiological relevance of a voltage-gated H+ channel in murine osteoclasts: phorbol myristate acetate induces cell acidosis and the channel activation. Journal of Bone and Mineral Research, 18, 2069-2076.
74. Morinaga, T., Nakagawa, N., Yasuda, H., Tsuda, E. & Higashio, K. (1998) Cloning and characterization of the gene encoding human osteoprotegerin/osteoclastogenesis-inhibitory factor. European Journal of Biochemistry, 254, 685-691.
75. Morrison, N.A., Qi, J.C., Tokita, A., Kelly, P.J., Crofts, L., Nguyen, T.V., Sambrook, P.N. & Eisman, J.A. (1994) Prediction of bone density from vitamin D receptor alleles. Nature, 367, 284-287.
76. Mundy, G.R. (1999) Cellular and molecular regulation of bone turnover. Bone, 24 (5 Suppl.), 35S-38S.
77. Nguyen, T.V., Pocock, N. & Eisman, J.A. (2000) Interpretation of bone mineral density measurement and its change. Journal of Clinical Densitometry, 3, 107-119.
78. Olivieri, N.F. (1999) The beta-thalassemias. New England Journal of Medicine, 341, 99-109.
79. Olivieri, N.F., Koren, G., Harris, J., Khattak, S., Freedman, M.H., Templeton, D.M., Bailey, J.D. & Reilly, B.J. (1992) Growth failure and bony changes induced by deferoxamine. American Journal of Pediatric Hematology and Oncology, 14, 48-56.
80. Olszynski, W.P., Shawn Davison, K., Adachi, J.D., Brown, J.P., Cummings, S.R., Hanley, D.A., Harris, S.P., Hodsman, A.B., Kendler, D., McClung, M.R., Miller, P.D. & Yuen, C.K. (2004) Osteoporosis in men: epidemiology, diagnosis, prevention, and treatment. Clinical Therapeutics, 26, 15-28.
81. Ortiz, C.O., Chen, B.K., Bale, L.K., Overgaard, M.T., Oxvig, C. & Conover, C.A. (2003) Transforming growth factor-beta regulation of the insulin-like growth factor binding protein-4 protease system in cultured human osteoblasts. Journal of Bone and Mineral Research, 18, 1066-1072.
82. Orvieto, R., Leichter, I., Rachmilewitz, E.A. & Margulies, J.Y. (1992) Bone density, mineral content, and cortical index in patients with thalassemia major and the correlation to their bone fractures, blood transfusions, and treatment with desferrioxamine. Calcified Tissue International, 50, 397-399.
83. Pennisi, P., Pizzarelli, G., Spina, M., Riccobene, S. & Fiore, C.E. (2003) Quantitative ultrasound of bone and clodronate effects in thalassemia-induced osteoporosis. Journal of Bone and Mineral Metabolism, 21, 402-408.
84. Perifanis, V., Vyzantiadis, T., Vakalopoulou, S., Tziomalos, K., Garypidou, V., Athanassiou-Metaxa, M. & Harsoulis, F. (2004) Treatment of beta-thalassaemia-associated osteoporosis with zoledronic acid. British Journal of Haematology, 125, 91-92 [letter].
85. Perrotta, S., Cappellini, M.D., Bertoldo, F., Servedio, V., Iolascon, G., D'Agruma, L., Gasparini, P., Siciliani, M.C. & Iolascon, A. (2000) Osteoporosis in beta-thalassaemia major patients: analysis of the genetic background. British Journal of Haematology, 111, 461-466.
86. Piga, A., Luzzatto, L., Capalbo, P., Gambotto, S., Tricta, F. & Gabutti, V. (1988) High-dose desferrioxamine as a cause of growth failure in thalassemic patients. European Journal of Haematology, 40, 380-381 [letter].
87. Pootrakul, P., Hungsprenges, S., Fucharoen, S., Baylink, D., Thompson, E., English, E., Lee, M., Burnell, J. & Finch, C. (1981) Relation between erythropoiesis and bone metabolism in thalassemia. New England Journal of Medicine, 304, 1470-1473.
88. Power, R.A., Iwaniec, U.T., Magee, K.A., Mitova-Caneva, N.G. & Wronski, T.J. (2004) Basic fibroblast growth factor has rapid bone anabolic effects in ovariectomized rats. Osteoporosis International, doi: 10.1007/s00198-004-1595-4.
89. Raiola, G., Galati, M.C., De Sanctis, V., Caruso Nicoletti, M., Pintor, C., De Simone, M., Arcuri, V.M. & Anastasi, S. (2003) Growth and puberty in thalassemia major. Journal of Pediatric Endocrinology and Metabolism, 16(Suppl. 2), 259-266.
90. Riggs, B.L. (2000) The mechanisms of estrogen regulation of bone resorption. Journal of Clinical Investigation, 106, 1203-1204.
91. Riggs, B.L., Khosla, S. & Melton, L.J. III (1998) A unitary model for involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. Journal of Bone and Mineral Research, 13, 763-773.
92. Rodda, C.P., Reid, E.D., Johnson, S., Doery, J., Matthews, R. & Bowden, D.K. (1995) Short stature in homozygous beta-thalassaemia is due to disproportionate truncal shortening. Clinical Endocrinology, 42, 587-592.
93. Roodman, G.D. (2004) Mechanisms of bone metastasis. New England Journal of Medicine, 350, 1655-1664.
94. Rucker, D., Ezzat, S., Diamandi, A., Khosravi, J. & Hanley, D.A. (2004) IGF-I and testosterone levels as predictors of bone mineral density in healthy, community-dwelling men. Clinical Endocrinology, 60, 491-499.
95. Simonet, W.S., Lacey, D.L., Dunstan, C.R., Kelley, M., Chang, M.S., Luthy, R., Nguyen, H.Q., Wooden, S., Bennett, L., Boone, T., Shimamoto, G., DeRose, M., Elliott, R., Colombero, A., Tan, H.L., Trail, G., Sullivan, J., Davy, E., Bucay, N., Renshaw-Gegg, L., Hughes, T.M., Hill, D., Pattison, W., Campbell, P., Sander, S., Van, G., Tarpley, J., Derby, P., Lee, R. & Boyle, W.J. (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell, 89, 309-319.
96. Smith, E.P., Boyd, J., Frank, G.R., Takahashi, H., Cohen, R.M., Specker, B., Williams, T.C., Lubahn, D.B. & Korach, K.S. (1994) Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. New England Journal of Medicine, 331, 1056-1061.
97. Soliman, A.T., El Banna, N., Abdel Fattah, M., El Zalabani, M.M. & Ansari, B.M. (1998) Bone mineral density in prepubertal children with beta-thalassemia: correlation with growth and hormonal data. Metabolism, 47, 541-548.
98. Stein, G.S. & Lian, J.B. (1993) Molecular mechanisms mediating proliferation/differentiation interrelationships during progressive development of the osteoblast phenotype. Endocrinology Reviews, 14, 424-442.
99. Suda, T., Nakamura, I., Jimi, E. & Takahashi, N. (1997) Regulation of osteoclast function. Journal of Bone and Mineral Research, 12, 869-879.
100. Teitelbaum, S.L. (2000) Bone resorption by osteoclasts. Science, 289, 1504-1508.
101. Todd, J.A. & Robinson, R.J. (2003) Osteoporosis and exercise. Post-graduate Medical Journal, 79, 320-323.
102. Uitterlinden, A.G., Burger, H., van Duijn, C.M., Huang, Q., Hofman, A., Birkenhager, J.C., van Leeuwen, J.P. & Pols, H.A. (2000) Adjacent genes, for COL2A1 and the vitamin D receptor, are associated with separate features of radiographic osteoarthritis of the knee. Arthritis & Rheumatism, 43, 1456-1464.
103. Uitterlinden, A.G., Weel, A.E., Burger, H., Fang, Y., van Duijn, C.M., Hofman, A., van Leeuwen, J.P. & Pols, H.A. (2001) Interaction between the vitamin D receptor gene and collagen type I alpha 1 gene in susceptibility for fracture. Journal of Bone and Mineral Research, 16, 379-385.
104. Uitterlinden, A.G., Fang, Y., Bergink, A.P., van Meurs, J.B., van Leeuwen, H.P. & Pols, H.A. (2002) The role of vitamin D receptor gene polymorphisms in bone biology. Molecular and Cellular Endocrinology, 197, 15-21.
105. Vanderkerken, K., Asosingh, K., Croucher, P. & Van Camp, B. (2003) Multiple myeloma biology: lessons from the 5TMM models. Immunological Reviews, 194, 196-206.
106. Vichinsky, E.P. (1998) The morbidity of bone disease in thalassemia. Annals of New York Academy of Sciences, 850, 344-348.
107. Voskaridou, E., Kyrtsonis, M.C., Terpos, E., Skordili, M., Theodoropoulos, I., Bergele, A., Diamanti, E., Kalovidouris, A., Loutradi, A. & Loukopoulos, D. (2001) Bone resorption is increased in young adults with thalassaemia major. British Journal of Haematology, 112, 36-41.
108. Voskaridou, E., Terpos, E., Spina, G., Palermos, J., Rahemtulla, A., Loutradi, A. & Loukopoulos, D. (2003) Pamidronate is an effective treatment for osteoporosis in patients with beta-thalassaemia. British Journal of Haematology, 123, 730-737.
109. Whedon, G.D. (1984) Disuse osteoporosis: physiological aspects. Calcified Tissue International, 36(Suppl. 1), 146-150.
110. Wonke, B. (1998) Bone disease in β-thalassaemia major. British Journal of Haematology, 103, 897-901.
111. Wonke, B. (2001) Clinical management of beta-thalassemia major. Seminars in Hematology, 38, 350-359.
112. Wonke, B., Jensen, C., Hanslip, J.J., Prescott, E., Lalloz, M., Layton, M., Erten, S., Tuck, S., Agnew, J.E., Raja, K., Davies, K. & Hoffbrand, A.V. (1998) Genetic and acquired predisposing factors and treatment of osteoporosis in thalassaemia major. Journal of Pediatric Endocrinology & Metabolism, 11 (Suppl. 3), 795-801.
113. World Health Organization (1994) Assessment of Fracture Risks and Its Application to Screening for Post-Menopausal Osteoporosis. Technical Report Series 843. WHO, Geneva.
114. Writing Group for the ISCD Position Development Conference (2004) Diagnosis of osteoporosis in men, premenopausal women, and children. Journal of Clinical Densitometry, 7, 17-26.