Additive Effects of Raloxifene and Alendronate on Bone Density and Biochemical Markers of Bone Remodeling in Postmenopausal Women with Osteoporosis

Abstract

Both raloxifene (RLX) and alendronate (ALN) can treat and prevent new vertebral fractures, increase bone mineral density (BMD), and decrease biochemical markers of bone turnover in postmenopausal women with osteoporosis. This phase 3, randomized, double-blind 1-yr study assessed the effects of combined RLX and ALN in 331 postmenopausal women with osteoporosis (femoral neck BMD T-score, less than -2). Women (aged< or = 75 yr; > or = 2 yr since their last menstrual period) received placebo, RLX 60 mg/d, ALN 10 mg/d, or RLX 60 mg/d and ALN 10 mg/d combined. At baseline, 6 and 12 months, BMD was measured by dual x-ray absorptiometry. The bone turnover markers serum osteocalcin, bone-specific alkaline phosphatase, and urinary N- and C-telopeptide corrected for creatinine were measured. The effects of RLX and ALN were considered to be independent and additive if the interaction effect was not statistically significant (P > 0.10) in a two-way ANOVA model. All changes in BMD and bone markers at 12 months were different between placebo and each of the active treatment groups, and between the RLX and RLX+ALN groups (P < 0.05). On average, lumbar spine BMD increased by 2.1, 4.3, and 5.3% from baseline with RLX, ALN, and RLX+ALN, respectively. The increase in femoral neck BMD in the RLX+ALN group (3.7%) was greater than the 2.7 and 1.7% increases in the ALN (P = 0.02) and RLX (P < 0.001) groups, respectively. The changes from baseline to 12 months in bone markers ranged from 7.1 to -16.0% with placebo, -23.8 to -46.5% with RLX, -42.3 to -74.2% with ALN, and -54.1 to -81.0% in the RLX+ALN group. RLX and ALN increased lumbar spine and femoral neck BMD, and decreased osteocalcin and C-telopeptide corrected for creatinine in an additive and independent manner, because the interaction effects were not significant. Although the ALN group had changes in BMD and bone markers that were approximately twice the magnitude as in the RLX group, it is not known how well these changes correlate to the clinical outcome of fracture. RLX+ALN reduced bone turnover more than either drug alone, resulting in greater BMD increment, but whether this difference reflects better fracture risk reduction was not assessed in this study.

Six and Twelve Month Changes in Bone Turnover are Related to Reduction in Vertebral Fracture Risk During 3 Years of Raloxifene Treatment in Postmenopausal Osteoporosis

“…Taken together with the fact that LSC for BMD may be estimated to be in the order of 3-4% [35], this may indicate that a substantial increase in BMD would be associated with a lowered fracture risk. It is well established that for clinical therapy regimens, the BMD response seen with raloxifene is significantly less than that seen with alendronate [9,11,37]. Because a large proportion of the BMD response seen during raloxifene therapy lies within the range of LSC, signal-to-noise ratio for this surrogate marker is far from its optimum.…”

Bone and glucose metabolism: A two-way street

“…Bisphosphonates are anti-resorptive treatments for osteoporosis that reduce bone formation markers, including osteocalcin (119). Total OC levels are reduced by 40–50%, and ucOC levels are likely reduced as well although only a few studies have investigated this directly.…”

Treatment of osteoporosis: Current status and recent advances

“…136 Selective estrogen-receptor modulators could be combined with a biphosphonate to enhance their effect on bone mass, although the costs could be prohibitive. 137 In a recent doubleblind study, the mean difference in BMD between raloxifene-treated patients and those taking placebo was 2.4% for the lumbar spine, 2.4% for the femur, and 2% for the total body, while total cholesterol decreased by 6.4% and LDL decreased by 10%. 138 However, there was no change in serum concentrations of HDL cholesterol or triglycerides, whereas both increase in women treated with estrogen.…”