A Four-Year Randomized Controlled Trial of Hormone Replacement and Bisphosphonate, Alone or in Combination, in Women with Postmenopausal Osteoporosis

Article · March 1998with18 Reads
DOI: 10.1016/S0002-9343(98)00029-1 · Source: PubMed
Hormone replacement therapy (HRT) with estrogen and treatment with bisphosphonates have been shown to increase bone mineral density (BMD) in postmenopausal women. This 4-year prospective randomized study was carried out to assess the effectiveness of the combined HRT plus etidronate on BMD in postmenopausal women with established osteoporosis. Seventy-two postmenopausal women (mean age 64.9+/-0.5 years) attending metabolic bone disease outpatient clinics with established osteoporosis were randomly allocated into one of four treatment groups and monitored for 4 years. All patients enrolled in this study including the control group (n=18) received 1.0 g elemental calcium and 400 units vitamin D per day. The HRT group (n=18) received cyclical estrogen and progesterone; the etidronate group (n=17) received intermittent cyclical etidronate; and the combined therapy group (n=19) received both HRT and etidronate. BMD was measured in the lumbar spine and the hip before treatment and at 2 and 4 years after treatment. Changes in height were recorded, and the occurrence of new vertebral fractures were documented in comparison with the baseline radiographic evaluation. In 40 patients (10 patients per group), analysis of bone histomorphometry was carried out after 4 years of treatment. In patients who received the combined therapy, BMD increased in the lumbar spine by 10.4% (P <0.001) and in the hip by 7.0% (P <0.001) at 4 years. For patients treated with ICE, these increases were 7.3% (P <0.001) and 0.9% (P <0.05), and with HRT, the increases were 7.0% (P <0.001) and 4.8% (P <0.01) in the vertebrae and femora, respectively. The group treated with calcium and vitamin D lost 2.5% (P <0.05) and 4.4% (P <0.01) of BMD in the vertebrae and femora, respectively, after 4 years. Patients who received combined therapy had significantly higher BMD in both the vertebrae and in the femora (P <0.05) in comparison with patients who were treated with HRT or etidronate alone after 4 years. In comparison with patients in the control group, there was a trend toward a lower rate of new vertebral fractures in the treatment groups. Height loss was significantly less in all three active treatment groups (HRT [P <0.001], etidronate [P <0.02], and combined therapy group [P <0.0001]), in comparison with the control group. The combined therapy group did not have a significant height loss, in comparison with the HRT (P <0.02) and the etidronate (P <0.001) groups. None of the patients had histomorphometric evidence of osteomalacia. This 4-year randomized study showed an additive effect of etidronate and HRT on hip and spine BMD in postmenopausal women with established osteoporosis.
    • Adequate supplementation of animals or humans with the NO precursor L -arginine could also be effective in prevention of bone losses [99] but the amount of L -arginine necessary to have these biological effects is high, making this approach impractical [10] . The role of combination therapies [47,85,97,100] needs to be investigated, especially the combination of NO donors with bisphosphonates [5] .
    File · Data · Dec 2015 · Osteoporosis International
    • The results were consistent across studies, both for the 1–3 year data (Fig. 3) and for the 4-year data – both reflected in a nonsignificant test of heterogeneity. However, the 4-year results were based on only 2 trials [10,11] with a sample size of 47. Furthermore, the effects at 1–3 years were larger in the 3 studies that followed patients for 4 years than those that did not, raising questions about the interpretation of the difference at 4 years.
    File · Data · Jul 2013 · Osteoporosis International
    • The decrease of estrogen353637 or the impaired responsiveness of bone to low sex steroid concentrations [38] during aging, and especially menopause, negatively affects bone health. Hormone replacement therapy (HRT) prevents bone loss and increases bone mass in postmenopausal women [39], but with additional side effects such as invasive breast cancer [40]. This peaked interest on the effectiveness of phytoestrogens on bone health promotion.
    [Show abstract] [Hide abstract] ABSTRACT: Vitamin D is known to increase Ca absorption in adults. However, the threshold vitamin D status to benefit Ca absorption is lower than the target vitamin D status for higher bone mineral density and lower fracture risk, pointing to another pathway for vitamin D to benefit bone. One possibility is by affecting osteoblast and osteoclasts directly. Vitamin D-related bone metabolism may also be affected by soy isoflavones, which selectively bind to the estrogen receptor β and may reduce bone loss in postmenopausal women. We discuss a possible synergistic effect of soy isoflavones and vitamin D on bone by affecting osteoblast and osteoclast formation and activity in postmenopausal women.
    Full-text · Article · Dec 2012
    • Fracture Location Nr of RCTs n RESULTS References Vertebral fracture 4 RCTs 11,842 RR=0.55; CI 95%: 0.46 to 0.66 (Wimalawansa, 1998; Mosekilde et al., 2000; Anderson et al., 1997; Lufkin et al., 1992
    Full-text · Chapter · Feb 2012 · Osteoporosis International
    • The results of the screening process are provided in the PRISMA diagram [25] inFigure 1 and the descriptions of the included studies are presented inTable 1. For the 9 drugs, 6 studies were for alendronate262728293031, 1 study for denosumab [32] , 8 studies for eti- dronate3334353637383940, 4 studies for ibandronate41424344, 1 study for raloxifene [45], 6 studies for risedronate464748495051, 2 studies for strontium [52,53] , 1 for teripara- tide [54], and 1 for zoledronic Acid [55] . The participants in the studies included 59,209 patients.
    [Show abstract] [Hide abstract] ABSTRACT: In the absence of head-to-head trials, indirect comparisons of randomized placebo-controlled trials may provide a viable option to assess relative efficacy. The purpose was to estimate the relative efficacy of reduction of fractures in post-menopausal women, and to assess robustness of the results. A systematic literature review of multiple databases identified randomized placebo-controlled trials with nine drugs for post-menopausal women. Odds ratio and 95% credibility intervals for the rates of hip, non-vertebral, vertebral, and wrist fractures for each drug and between drugs were derived using a Bayesian approach. A drug was ranked as the most efficacious if it had the highest posterior odds ratio, or had the highest effect size. 30 studies including 59,209 patients reported fracture rates for nine drugs: alendronate (6 studies), denosumab (1 study), etidronate (8 studies), ibandronate (4 studies), raloxifene (1 study), risedronate (7 studies), strontium (2 study), teriparatide (1 study), and zoledronic acid (1 study). The drugs with the highest probability of reducing non-vertebral fractures was etidronate and teriparatide while the drugs with the highest probability of reducing vertebral, hip or wrist fractures were teriparatide, zoledronic acid and denosumab. The drugs with the largest effect size for vertebral fractures were zoledronic acid, teriparatide and denosumab, while the drugs with the highest effect size for non-vertebral, hip or wrist fractures were alendronate or risedronate. Estimates were consistent between Bayesian and classical approaches. Teriparatide, zoledronic acid and denosumab have the highest probabilities of being most efficacious for non-vertebral and vertebral fractures, and having the greatest effect sizes. The estimates from indirect comparisons were robust to differences in methodology.
    Full-text · Article · Sep 2011
    • Bisphosphonate is one of the most effective drugs currently available for suppressing bone resorption. Naturally, combination therapies with other antiresorptive or formative agents have been investigated: PTH [1][2][3], vitamin D [2, 4], estrogen [5][6][7], and other agents [8]. Risedronate, a pyridinyl (amino) bisphosphonate, significantly reduces the risk of hip fracture among elderly women with confirmed osteoporosis and if combined with estrogen or raloxifene, produces greater gains in bone mass in comparison to single-agent treatment [9] .
    [Show abstract] [Hide abstract] ABSTRACT: Prior 8-week treatment with menatetrenone, MK-4, followed by 8-week risedronate prevented the shortcomings of individual drugs and significantly increased the strength of ovariectomized ICR mouse femur compared to the ovariectomized (OVX) controls. Neither MK-4 following risedronate nor the concomitant administration may be recommended because they brought the least beneficial effect. The objective of this study was to determine the best combinatory administration of risedronate at 0.25 mg/kg/day (R) with vitamin K(2) at approximately 100 microg MK-4/kg/day (K) to improve strength of osteoporotic mouse bone. Thirteen-week-old ICR mice, ovariectomized at 9-week, were treated for 8 weeks with R, K, or R plus K (R/K), and then, either the treatment was withdrawn (WO) or switched to K or R in the case of R and K. After another 8 weeks, the mice were killed, and mechanical tests and analyses of femur properties by peripheral quantitative computed tomography, microfocus X-ray tube computed tomography, and confocal laser Raman microspectroscopy were carried out. The K to R femur turned out superior in parameters tested such as material properties, bone mineral density, BMC, trabecular structure, and geometry of the cortex. The increased cross-sectional moment of inertia, which occurred after K withdrawal, was prevented by risedronate in K to R. In addition to K to R, some properties of R to WO diaphysis and K to WO epiphysis were significantly better than OVX controls. Prior treatment with MK-4 followed by risedronate significantly increased femur strength in comparison to the OVX controls.
    Full-text · Article · Apr 2009
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