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ISSN 0188-9796 (Print)

2000, Number 2

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Rev Endocrinol Nutr 2000; 8 (2)

Osteoporosis in patients with systemic lupus erythematosus under long-term treatment with methotrexate

Canseco-Lima J, Martínez-Wagner R, Dent-Alvarado H, Mercado-Delgado E, Alvarado-Contreras G, Ramírez-Diez J, González-Amaro R, Abud-Mendoza C

Language: Spanish
References: 64
Page: 56-61
PDF size: 183.81 Kb.


ABSTRACT

Background: Patients with Sistemic lupus eritematosus (SLE) frequently have to receive steroids for the control of their disease; also, they require immunomodulators such as Mtx to control SLE’s manifestations as well as to decrease the dose of steroids in order to avoid their side effects. These drugs predispose to OP. We developed this prospective and transversal study to assess the presence of OP in patients with SLE treated with prednisone (Pdn), Mtx, calcium and Vitamin D, and its potential association with the activity index (Mex-SLEDAI), dose and time taking Pdn and Mtx. We evaluate the potential association of OP in patients with SLE under long term Pdn and Mtx treatment. Methods: We studied 26 patients with SLE who upon diagnosis began to receive small oral doses of Mtx weekly. The patients included were those who had been takin Mtx for at least 1 year under doses of 7.5 to 25 mg weekly. All of them were evaluated with clinical data, laboratory and radiocubital densitometry (DXA-DTX-200). We diagnosed OP in our patients when they had a standard deviation of -2.5 out of the normal values (from -2.5 to -1 standard deviations) given by the WHO. All of the patients received calcium and Vitamin D. Results: The majority of the group were female (24/26) and 4 of the 24 were in the postmenopause category but did not receive any hormonal replacement therapy. From the group 23% had osteopenia and 15% OP, while 62% had a normal bone densitometry. OP was found more frequently than osteopenia and normal bone densitometry in older patients (41 ± 17 yrs) and with 8 yrs evolution of SLE, whereas osteopenia occurred more frequently in the 36 ± 12 yrs range at 6 yrs of evolution of the disease with normal bone densitometry following in the 27 ± 9 yrs range with 4 yrs of disease evolution. The Pdn administration time did not show any difference between the patients with a normal bone densitometry or those with osteopenia (4 yrs), but it was higher in those patients with OP (8 yrs). This same tendency was seen in the Mtx administration time (3.8 vs 5.75 yrs) and in the cumulative doses of Mtx (3 vs 4 g). The patients with SLE who had a normal bone densitometry has cumulative doses of Pdn of 31.4 ± 51.5 mg which were higher than those with osteopenia (12.5 ± 6 mg) but smaller than those with OP (78 ± 118). Conclusions: Patients with SLE under steroid medication have more proclivity to develop OP. This osteo-metabolic problem cannot be avoided by the co-administration of calcium and vitamin D. The addition of Mtx may increase the risk of OP; however, it decreases SLE activity as well as the steroid dose needed. economic resources.


REFERENCES

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  2. Ramos-Remus C, Sibley J, Russell AS. Steroids in rheumatoid arthritis: the honeymoon revisited. J Rheumatol 1992; 19: 667. 3. Hahn TJ, Haistead LR, Teitelbaum SL et al. Altered mineral metabolism in glucocorticoid-induced osteopenia: effect

  3. of 25-hydroxyvitamin D administration. J Clin Invest 1979; 64: 655.

  4. Lukert BP, Raisz LG. Glucocorticoid-induced osteoporosis pathogenesis and management. Ann Intern Med 1990: 112-352.

  5. Mazanec DJ, Grisanti JM. Drug-induced osteoporosis. Cleveland Clin J Med 1989; 56: 297-303.

  6. Recomendations for the prevention and treatment of glucocorticoid-induced osteoporosis. American College of Rheumatology Task Force on Osteoporosis Guidelines. Arthritis Rheum 1996; 39: 1791.

  7. Weinstein RS, Jika RL, Parfitt AM, Manolagas SC. Inhibition of osteogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest 1998; 102:

  8. 274-82.

  9. Kipen Y, Littlejohn GO, Morand EF. Methotrexate use in systemic lupus erythematosus. Lupus 1997; 6: 385-9.

  10. Gansauge S, Breitbart A, Rinaldi N, Schwarz-Eywill M. Methotrexate in patients with moderate systemic lupus erythematosus (exclusion of renal and central nervous system disease). Ann Rheum Dis 1997; 56: 382-5.

  11. Preston SJ, Diamond T, Scott A, Laurent MR. Methotrexate osteopathy in rheumatic disease. Ann Rheum Dis 1993; 52: 582-5.

  12. Friedlaender GE, Tross RB, Doganis AC, Kirkwood JM, Baaron R. Effects of chemotherapeutic agents on bone. J Bone Joint Surg 1984; 60a: 602-7.

  13. May KP, West SG, McDermott MT, Huffer WE. The effect of low dose methotrexate on bone metabolism and histomorphometry in rats. Arthritis Rheum 1994; 37:

  14. 201-6.

  15. Tan EM, Cohen AS, Fries J et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271-7.

  16. Guzmán J, Cardiel MH, Arce-Salinas A et al. Measurement of disease activity in systemic lupus erythematosus. Prospective validation of 3 clinical indices. J Rheumatol 1992; 19: 1551-8.

  17. Glucocorticoid induced osteoporosis. In osteoporosis: R Marcus, D Feldman, and J Kelsey editors. Academic press. San Diego, CA: 801-20.

  18. Morand EF. Corticosteroids in the treatment of rheumatologic diseases. Curr Op Rheumatol 2000; 12: 171-177.

  19. West SG. Methotrexate hepatotoxicity. Rheum Dis Clin North Am 1997; 23(4): 883-915.

  20. Iqbal MP. Accumulation of methotrexate in human tissues following high-dose methotrexate therapy. JPMA J Pak Med Assoc 1998; 48(11): 341-3.

  21. Weinblatt ME. Methotrexate, in Textbook of Rheumatology, by Kelley, Harris, Ruddy and Sledge, eds., fifth ed., 1997: 771-86.

  22. Hashkes PJ, Balistreri WF, Bove KE, Ballard ET, Passo MH. The relationship of hepatotoxic risk factors and liver histology in methotrexate therapy for juvenile rheumatoid arthritis. J Pediatr 1999; 134(1): 47-52.

  23. Buckley LM, Leib ES, Cartularo KS, Vacek PM, Cooper SM. Effects of low dose methotrexate on the bone mineral density of patients with rheumatoid arthritis. J Rheumatol 1997; 24: 1489-94.

  24. Schwartz AM, Leonidas JC. Methotrexate Osteopathy. Skeletal Radiol 1984; 11: 13-6.

  25. Lukert BP, Raisz LG. Glucocorticoid induced-osteoporosis. Rheum Dis Clin North Am 1994; 20: 629-50.

  26. Manalagas SC, Jilka R. Bone marrow, cytokines and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. N Engl J Med 1995; 332: 305-11.

  27. Segal LG, Lane NE. Osteoporosis and systemic lupus erythematosus. Etiology and treatment strategies. Ann Intern Med 1996; 147: 281-9.

  28. Seitz M, Hunstein W. Enhanced prostanoid release from monocytes of patients with rheumatoid arthritis and active systemic lupus erythematosus. Ann Rheum Dis 1985; 44: 438-45.

  29. Tanaka Y, Watanabe K, Suzuki M et al. Spontaneous production of bone-resorbing lymphokines by B-cells in patients with systemic lupus erythematosus. J Clin Immunol 1989; 9: 415-20.

  30. Abud-Mendoza C, Sturbaum AK, Vazquez-Compean et al. Methotrexate therapy in childhood systemic lupus erythematosus. J Rheumatol 1993; 20: 731-3.

  31. Abud-Mendoza C, Cuevas E, Gonzalez-Amaro R. Long-term methotrexate therapy in systemic lupus erythematosus with renal involvement. Arthritis Rheum 1998 (suppl); 41: 463.

  32. Saag K, Emkey R, Schnitzer TJ, Brown JP, Hawkins F, Goemaere S, Thamsborg G et al. Alendronate for the prevention and treatment glucocorticoid-induced osteoporosis. N Engl J Med 1998; 339: 292-9

  33. Cunnane G, Lane EN. Steroid-induced osteoporosis in systemic lupus erythematosus. Rheum Dis Clin Noth Am 2000; 26: 311-29.

  34. Teichmann J, Lange U, Stracke H, Federlin K, Bretzel RG. Bone metabolism and bone mineral density of systemic lupus erythematosus at the time of diagnosis. Rheumatol Int 1999; 18: 137-40.

  35. Ramos-Remus C, Sibley J, Russell AS. Steroids in rheumatoid arthritis: the honeymoon revisited. J Rheumatol 1992; 19: 667.

  36. Hahn TJ, Haistead LR, Teitelbaum SL et al. Altered mineral metabolism in glucocorticoid-induced osteopenia: effect of 25-hydroxyvitamin D administration. J Clin Invest 1979; 64: 655.

  37. Lukert BP, Raisz LG. Glucocorticoid-induced osteoporosis pathogenesis and management. Ann Intern Med 1990: 112-352.

  38. Mazanec DJ, Grisanti JM. Drug-induced osteoporosis. Cleveland Clin J Med 1989; 56: 297-303.

  39. Recomendations for the prevention and treatment of glucocorticoid-induced osteoporosis. American College of Rheumatology Task Force on Osteoporosis Guidelines. Arthritis Rheum 1996; 39: 1791.

  40. Weinstein RS, Jika RL, Parfitt AM, Manolagas SC. Inhibition of osteogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest 1998; 102: 274-82.

  41. Kipen Y, Littlejohn GO, Morand EF. Methotrexate use in systemic lupus erythematosus. Lupus 1997; 6: 385-9.

  42. Gansauge S, Breitbart A, Rinaldi N, Schwarz-Eywill M. Methotrexate in patients with moderate systemic lupus erythematosus (exclusion of renal and central nervous system disease). Ann Rheum Dis 1997; 56: 382-5.

  43. Preston SJ, Diamond T, Scott A, Laurent MR. Methotrexate osteopathy in rheumatic disease. Ann Rheum Dis 1993; 52: 582-5.

  44. Friedlaender GE, Tross RB, Doganis AC, Kirkwood JM, Baaron R. Effects of chemotherapeutic agents on bone. J Bone Joint Surg 1984; 60a: 602-7.

  45. May KP, West SG, McDermott MT, Huffer WE. The effect of low dose methotrexate on bone metabolism and histomorphometry in rats. Arthritis Rheum 1994; 37: 201-6.

  46. Tan EM, Cohen AS, Fries J et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271-7.

  47. Guzmán J, Cardiel MH, Arce-Salinas A et al. Measurement of disease activity in systemic lupus erythematosus. Prospective validation of 3 clinical indices. J Rheumatol 1992; 19: 1551-8.

  48. Glucocorticoid induced osteoporosis. In osteoporosis: R Marcus, D Feldman, and J Kelsey editors. Academic press. San Diego, CA: 801-20.

  49. Morand EF. Corticosteroids in the treatment of rheumatologic diseases. Curr Op Rheumatol 2000; 12: 171-177.

  50. West SG. Methotrexate hepatotoxicity. Rheum Dis Clin North Am 1997; 23(4): 883-915.

  51. Iqbal MP. Accumulation of methotrexate in human tissues following high-dose methotrexate therapy. JPMA J Pak Med Assoc 1998; 48(11): 341-3.

  52. Weinblatt ME. Methotrexate, in Textbook of Rheumatology, by Kelley, Harris, Ruddy and Sledge, eds., fifth ed., 1997: 771-86.

  53. Hashkes PJ, Balistreri WF, Bove KE, Ballard ET, Passo MH. The relationship of hepatotoxic risk factors and liver histology in methotrexate therapy for juvenile rheumatoid arthritis. J Pediatr 1999; 134(1): 47-52.

  54. Buckley LM, Leib ES, Cartularo KS, Vacek PM, Cooper SM. Effects of low dose methotrexate on the bone mineral density of patients with rheumatoid arthritis. J Rheumatol 1997; 24: 1489-94.

  55. Schwartz AM, Leonidas JC. Methotrexate Osteopathy. Skeletal Radiol 1984; 11: 13-6.

  56. Lukert BP, Raisz LG. Glucocorticoid induced-osteoporosis. Rheum Dis Clin North Am 1994; 20: 629-50.

  57. Manalagas SC, Jilka R. Bone marrow, cytokines and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. N Engl J Med 1995; 332: 305-11.

  58. Segal LG, Lane NE. Osteoporosis and systemic lupus erythematosus. Etiology and treatment strategies. Ann Intern Med 1996; 147: 281-9.

  59. Seitz M, Hunstein W. Enhanced prostanoid release from monocytes of patients with rheumatoid arthritis and active systemic lupus erythematosus. Ann Rheum Dis 1985; 44: 438-45.

  60. Tanaka Y, Watanabe K, Suzuki M et al. Spontaneous production of bone-resorbing lymphokines by B-cells in patients with systemic lupus erythematosus. J Clin Immunol 1989; 9: 415-20.

  61. Abud-Mendoza C, Sturbaum AK, Vazquez-Compean et al. Methotrexate therapy in childhood systemic lupus erythematosus. J Rheumatol 1993; 20: 731-3.

  62. Abud-Mendoza C, Cuevas E, Gonzalez-Amaro R. Long-term methotrexate therapy in systemic lupus erythematosus with renal involvement. Arthritis Rheum 1998 (suppl); 41: 463.

  63. Saag K, Emkey R, Schnitzer TJ, Brown JP, Hawkins F, Goemaere S, Thamsborg G et al. Alendronate for the prevention and treatment glucocorticoid-induced osteoporosis. N Engl J Med 1998; 339: 292-9

  64. Cunnane G, Lane EN. Steroid-induced osteoporosis in systemic lupus erythematosus. Rheum Dis Clin Noth Am 2000; 26: 311-29.




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