Abstract
We studied the effect of 1-year transdermal estrogen replacement therapy (ERT) on bone mineral density (BMD) and biochemical markers of bone turnover in osteopenic postmenopausal systemic lupus erythematosus (SLE) patients in a randomized, double-blind, placebo-controlled trial. SLE patients were randomly allocated to treatment (estradiol; 50 μg transdermal 17β-estradiol; n=15) or placebo (n=17) group. Both groups received 5 mg continuous oral medroxyprogesterone acetate, 500 mg calcium and 400 IU vitamin D3. L1–L4 spine (LS), left femur and total hip BMD were measured at baseline and at 6 and 12 months. Serum osteocalcin (OC) and degradation products of C-terminal telopeptides of type-I collagen (CTx) levels were measured at baseline and 3, 6, 9, and 12 months. There was a significant difference in the percentage change of LS BMD at 6 months between the two groups (103.24±3.74% (estradiol group) vs 98.99±3.11% (placebo group); P<0.005). There was a significant decrease within the estradiol group in the CTx levels between baseline and all subsequent visits (P<0.05). There was no significant difference in SLE disease activity index, Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) damage index and corticosteroid dose during the study period. Transdermal estradiol may prevent bone loss in postmenopausal SLE women at the lumbar spine and femur, with no increase in disease activity among postmenopausal SLE women receiving transdermal ERT. The high dropout rate (8/15) leads us to the conclusion that efficacy of HRT in a high-risk group such as SLE women can be attained only in a small number of patients, provided all inclusion/exclusion criteria are strictly adhered to.
Similar content being viewed by others
References
Gladman DD, Ginzler E, Goldsmith C, et al (1996) The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum 39:363–369
Costallat LT, Coimbra AM (1994) Systemic lupus erythematosus. Clinical and laboratory aspects related to age at disease onset. Clin Exp Rheumatol 12:603–607
Abu-Shakra M, Urowitz MB, Gladman DD, Gough J (1995) Mortality studies in systemic lupus erythematosus. Results from a single center. II. Predictive variables for mortality. J Rheumatol 22:1265–1270
Ward MM, Pyun E, Studenski S (1995) Long-term survival in systemic lupus erythematosus. Patient characteristics associated with poorer outcomes. Arthritis Rheum 38:274–282
Kiss E, Regeczy N, Szegedi G (1999) Systemic lupus erythematosus survival in Hungary. Results from a single centre. Clin Exp Rheumatol 17:171–177
Petri M, Robinson C (1997) Oral contraceptives and systemic lupus erythematosus. Arthritis Rheum 40:797–803
Julkunen HA (1991) Oral contraceptives in systemic lupus erythematosus: side-effects and influence on the activity of SLE. Scand J Rheumatol 20:427–433
Mok CC, Lau CS, Ho CT, Lee KW, Mok MY, Wong RW (1998) Safety of hormonal replacement therapy in postmenopausal patients with systemic lupus erythematosus. Scand J Rheumatol 27:342–349
Buyon JP (1998) Hormone replacement therapy in postmenopausal women with systemic lupus erythematosus. J Am Med Women Assoc 53:13–17
Kreidstein S, Urowitz MB, Gladman DD Gough J (1997) Hormone replacement therapy in systemic lupus erythematosus. J Rheumatol 24:2149–2152
Arden NK, Lloyd ME, Spector TD, Hughes GR (1994) Safety of hormone replacement therapy (HRT) in systemic lupus erythematosus (SLE). Lupus 3:11–13
Lautenbach GL, Petri M (1999) Women’s health. Rheum Dis Clin North Am. 25:539–565
Swaak AJ (1995) Clinical features of systemic lupus erythematosus patients with a disease duration more than 10 years. Rheumatol Eur S2:223–225
Mok CC, Lau CS, Wong RW (2001) Use of exogenous estrogens in systemic lupus erythematosus. Semin Arthritis Rheum. 30:426–235
Kipen Y, Buchbinder R, Forbes A, Strauss B, Littlejohn G, Morand E (1997) Prevalence of reduced bone mineral density in systemic lupus erythematosus and the role of steroids. J Rheumatol 24:1922–1929
Hansen M, Halberg P, Kollerup G, et al (1998) Bone metabolism in patients with systemic lupus erythematosus. Effect of disease activity and glucocorticoid treatment. Scand J Rheumatol 27:197–206
Teichmann J, Lange U, Stracke H, Federlin K, Bretzel RG (1999) Bone metabolism and bone mineral density of systemic lupus erythematosus at the time of diagnosis. Rheumatol Int 18:137–140
Gilboe IM, Kvien TK, Haugeberg G, Husby G (2000) Bone mineral density in systemic lupus erythematosus: comparison with rheumatoid arthritis and healthy controls. Ann Rheum Dis 59:110–115
Lakshminarayanan S, Walsh S, Mohanraj M, Rothfield N (2001) Factors associated with low bone mineral density in female patients with systemic lupus erythematosus. J Rheumatol 28:102–108
Becker A, Fischer R, Scherbaum WA, Schneider M (2001) Osteoporosis screening in systemic lupus erythematosus: impact of disease duration and organ damage. Lupus 10:809–814
Bhattoa HP, Bettembuk P, Balogh A, Szegedi G, Kiss E (2002) Bone mineral density in women with systemic lupus erythematosus. Clin Rheumatol 21:135–141
Kung AW, Chan TM, Lau CS, Wong RW, Yeung SS (1999) Osteopenia in young hypogonadal women with systemic lupus erythematosus receiving chronic steroid therapy: a randomized controlled trial comparing calcitriol and hormonal replacement therapy. Rheumatology (Oxford) 38:1239–1244
Grady D, Herrington D, Bittner V, et al (2002) Cardiovascular disease outcomes during 6.8 years of hormone therapy: heart and estrogen/progestin replacement study follow-up (HERS II). JAMA 288:49–57
Hulley S, Furberg C, Barrett-Connor E, et al (2002) Noncardiovascular disease outcomes during 6.8 years of hormone therapy: heart and estrogen/progestin replacement study follow-up (HERS II). JAMA 288:58–66
Hochberg M (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725–1734
Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 35:630–640
Lukert BP, Johnson BE, Robinson RG (1992) Estrogen and progesterone replacement therapy reduces glucocorticoid-induced bone loss. J Bone Miner Res 7:1063–1069
Hall GM, Daniels M, Doyle DV Spector TD (1994) Effects of hormone replacement therapy on bone mass in rheumatoid arthritis patients with and without steroids. Arthritis Rheum 37:1499–1505
Delmas PD (2002) Markers of bone turnover for monitoring treatment of osteoporosis with antiresorptive drugs. Osteoporos Int [Suppl 6]:S66–76
Post MS, Christella M, Thomassen LG, Van Der Mooren MJ, Van Baal WM, Rosing J, Kenemans P, Stehouwer CD (2003) Effect of oral and transdermal estrogen replacement therapy on hemostatic variables associated with venous thrombosis: a randomized, placebo-controlled study in postmenopausal women. Arterioscler Thromb Vasc Biol 23:1116–1121
Urowitz MB, Gladmann DD (2000) Accelerated atheroma in lupus—background. Lupus 9:161–165
Petri M (2001) Exogenous estrogens in systemic lupus erythematosus: oral contraceptives and hormone replacement therapy. Lupus 10:222–226
Petri MA, Lahita RG, van Vollenhoven RF, et al (2002) Effects of prasterone on corticosteroid requirements of women with systemic lupus erythematosus. Arthritis Rheum 46:1820–1829
Ettinger B, Black DM, Mitlak BH, et al (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene. Results from a 3-year randomized clinical trial. JAMA 282:637–645
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bhattoa, H.P., Bettembuk, P., Balogh, A. et al. The effect of 1-year transdermal estrogen replacement therapy on bone mineral density and biochemical markers of bone turnover in osteopenic postmenopausal systemic lupus erythematosus patients: a randomized, double-blind, placebo-controlled trial. Osteoporos Int 15, 396–404 (2004). https://doi.org/10.1007/s00198-003-1553-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00198-003-1553-6