Effect of raloxifene combined with monofluorophosphate as compared with monofluorophosphate alone in postmenopausal women with low bone mass: a randomized, controlled trial
Effect of raloxifene combined with monofluorophosphate as compared with monofluorophosphate alone in postmenopausal women with low bone mass a randomized, controlled trial.pdf
raloxifene; fluoride; BMD; bone markers; fractures; osteoporosis
Abstract :
[en] Raloxifene effectively reduces the incidence of vertebral fractures in patients with postmenopausal osteoporosis. Recent data suggest that low-dose monofluorophosphate (MFP) plus calcium reduces the vertebral fracture rate in postmenopausal women with moderate osteoporosis. The objective of this study was to evaluate the combination of raloxifene and MFP in the treatment of postmenopausal women with osteopenia, osteoporosis and severe osteoporosis. A total of 596 postmenopausal women with osteopenia, osteoporosis and severe osteoporosis (mean femoral neck T-score of -2.87 SD) were randomized to treatment with 60 mg/day raloxifene HCl and 20 mg/day fluoride ions (as MFP) or 20 mg/day fluoride and placebo for 18 months. All patients received calcium (1000 mg/day) and vitamin D (500 IU/day) supplements. Changes in bone mineral density (BMD), as primary endpoint, and the rate of osteoporotic fractures and biochemical markers, as secondary endpoints, were assessed. As compared with MFP, raloxifene plus MFP was associated with significantly greater mean increases in the BMD of the femoral neck (1.37% versus 0.33%; P=0.004), total hip (0.89% versus -0.42%; P<0.001) and lumbar spine (8.80% versus 5.47% P<0.001). In the raloxifene plus MFP group, 16 patients sustained 17 osteoporotic fractures, as compared with 22 patients sustaining 34 incident osteoporotic fractures in the MFP group (P=0.313). One patient in the raloxifene plus MFP group sustained multiple osteoporotic fractures, as compared with eight patients in the MFP group (P=0.020). MFP alone significantly increased the serum bone alkaline phosphatase (bone ALP) and the urinary C-terminal crosslinking telopeptide of type I collagene (U-CTX). The addition of raloxifene in the combination arm blunted the rise in bone ALP, which remained nevertheless significant, and abolished the increase in U-CTX. The combination of raloxifene with MFP was generally well tolerated. This study demonstrates that, in postmenopausal women with osteopenia, osteoporosis and severe osteoporosis, the combination therapy of raloxifene plus MFP favorably influences the BMD and the bone formation and resorption balance, and may reduce the risk of multiple osteoporotic fractures compared to MFP alone.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Epidémiologie et santé publique
Felsenberg, D.
Pavo, I.
Stepan, J.
Payer, J.
Resch, H.
Gluer, C. C.
Muhlenbacher, D.
Quail, D.
Schmitt, H.
Nickelsen, T.
Language :
English
Title :
Effect of raloxifene combined with monofluorophosphate as compared with monofluorophosphate alone in postmenopausal women with low bone mass: a randomized, controlled trial
Publication date :
September 2003
Journal title :
Osteoporosis International
ISSN :
0937-941X
eISSN :
1433-2965
Publisher :
Springer-Verlag London Ltd, Godalming, United Kingdom
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. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 282:637-645
Mamelle N, Meunier PJ, Dusan R et al. (1988) Risk-benefit ratio of sodium fluoride treatment in primary vertebral osteoporosis. Lancet 2:361-365
Heaney RP, Baylink DJ, Johnston CC Jr et al. (1989) Fluoride therapy for the vertebral crush fracture syndrome. A status report. Ann Int Med 111:678-680
Riggs BL, Hodgson SF, O'Fallon WM et al. (1990) Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis. N Engl J Med 322:802-809
Kleerekoper M, Peterson EL, Nelson DA et al. (1991) A randomized trial of sodium fluoride as a treatment for postmenopausal osteoporosis. Osteoporos Int 1:155-161
Kanis JA (1993) Treatment of symptomatic osteoporosis with fluoride. Am J Med 95:S53-S61
Riggs BL, O'Fallon WM, Lane A et al. (1994) Clinical trial of fluoride therapy in postmenopausal osteoporotic women: extended observations and additional analysis. J Bone Miner Res 9:265-275
Pak CY, Sakhaee K, Adams-Huet B et al. (1995) Treatment of postmenopausal osteoporosis with slow-release sodium fluoride. Final report of a randomized controlled trial. Ann Int Med 123:401-408
Meunier PJ, Sebert JL, Reginster JY et al. (1998) Fluoride salts are no better prevention at preventing new vertebral fractures than calcium-vitamin D in postmenopausal osteoporosis: the FAVOS study. Osteoporos Int 8:4-12
Reginster JY, Meurmans L, Zegels B et al. (1998) The effect of sodium monofluorophosphate plus calcium on vertebral fracture rate in postmenopausal women with moderate osteoporosis. Ann Int Med 129:1-8
Ringe JD, Dorst A, Kipshoven C et al. (1998) Avoidance of vertebral fractures in men with idiopathic osteoporosis by a three year therapy with calcium and low-dose intermittent monofluorophosphate. Osteoporos Int 8:47-52
Ringe JD, Kipshoven C, Coster A, Umbach R (1999) Therapy of established postmenopausal osteoporosis with monofluorophosphate plus calcium: dose-related effects on bone density and fracture rate. Osteoporos Int 9:171-178
Lindsay R, Nieves J, Formica C et al. (1997) Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis. Lancet 350:550-555
Neer RM, Arnaud CD, Zanchetta JR et al. (2001) Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434-1441
Haguenauer D, Welch V, Shea B et al. (2000) Fluoride for the treatment of postmenopausal osteoporotic fractures: a meta-analysis. Osteoporos Int 11:727-738
Balena R, Kleerekoper M, Foldes JA et al. (1998) Effects of different regimens of sodium fluoride treatment for osteoporosis on the structure, remodeling and mineralization of bone. Osteoporos Int 8:428-435
Farley JR, Wergedal JE, Baylink DJ (1983) Fluoride directly stimulates proliferation and alkaline phosphatase activity of bone-forming cells. Science 222:330-332
Lu Y, Ye K, Mathur AK et al. (1997) Comparative calibration without a gold standard. Stat Med 16:1889-1905
Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137-1148
Garnero P, Delmas PD (1993) Assessment of the serum levels of bone alkaline phosphatase with a new immunoradiometric assay in patients with metabolic bone disease. J Clin Endocrinol Metab 77:1046-1053
Garnero P, Gineyts E, Riou JP, Delmas PD (1994) Assessment of bone resorption with a new marker of collagen degradation in patients with metabolic bone disease. J Clin Endocrinol Metab 79:780-785
Lane NE, Sanchez S, Genant HK, Jenkins DK, Arnaud CD (2000) Short-term increases in bone turnover markers predict parathyroid hormone-induced spinal bone mineral density gains in postmenopausal women with glucocorticoid-induced osteoporosis. Osteoporos Int 11:434-442
Alexandersen P, Riis BJ, Christiansen C (1999) Monofluorophosphate combined with hormone replacement therapy induces a synergistic effect on bone mass by dissociating bone formation and resorption in postmenopausal women: a randomised study. J Clin Endocrinol Metab 84:3013-3020
Reginster JY, Agnusdei D, Gennari C, Kicovic PM (1999) Association of tibolone and fluoride displays a pronounced effect on bone mineral density in postmenopausal osteoporotic women. Gynecol Endocrinol 13:361-368
Eastell R, Robins SP, Colwell T, Assiri AM, Riggs BL, Russell RG (1993) Evaluations of bone turnover in type I osteoporosis using biochemical markers specific for both bone formation and bone resorption. Osteoporos Int 3:255-260
Sarkar S, Mitlak BH, Wong M et al. (2002) Relationships between bone mineral density and incident vertebral fracture risk with raloxifene therapy. J Bone Miner Res 17:1-10
Maricic M, Adachi JD, Sarkar S et al. (2002) Early effects of raloxifene on clinical vertebral fractures at 12 months in postmenopausal women with osteoporosis. Arch Int Med 162:1140-1143