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AbstractObjectives:The authors conducted a randomized controlled trial to clarify the efficacy and safety of alendronate plus alfacalcidol versus alendronate alone in a clinical setting.Research design and methods:Eligible patients were postmenopausal women with severe osteoporosis who were aged 70 years or older and had several risk factors for incident fractures. The primary endpoint was prevention of incident fractures, and the anti-fracture efficacy was evaluated in relation to the baseline serum 25(OH)D level.Results:A total of 2164 patients were randomized to alendronate plus alfacalcidol (combination therapy) or alendronate alone (monotherapy). Although the overall difference in the incidence of vertebral fracture between the two groups was not significant, the combination therapy group had a significantly reduced risk of vertebral fractures after the first 6 months (HR, 0.53). In subgroup analyses, the combination therapy group was superior in the strata of number of prevalent vertebral fractures of ≥2 (HR, 0.51) and grade 3 of prevalent vertebral fractures (HR, 0.55). The rate of non-vertebral weight-bearing bone fractures was significantly lower in the combination therapy group than in the monotherapy group during the follow-up period (HR, 0.31). A lower baseline 25(OH)D level was associated with a higher incidence of non-vertebral weight-bearing bone fractures (HR, 3.42) despite alendronate use. Although one patient given the combination therapy had mild hypercalcemia, serious hypercalcemia and unknown adverse events were not encountered. Because of the limitations presented in this study, these results may not apply to female patients with longer than 2 years of treatments, and to male osteoporosis patients.Conclusions:The combination therapy was no more effective for overall vertebral fracture prevention. However, subgroup analysis has shown that it was more effective for fracture prevention in patients with severe vertebral deformity, multiple prevalent vertebral fractures, and for non-vertebral weight-bearing bone fracture prevention. [ABSTRACT FROM AUTHOR]

Objectives:The authors conducted a randomized controlled trial to clarify the efficacy and safety of alendronate plus alfacalcidol versus alendronate alone in a clinical setting.Research design and methods:Eligible patients were postmenopausal women with severe osteoporosis who were aged 70 years or older and had several risk factors for incident fractures. The primary endpoint was prevention of incident fractures, and the anti-fracture efficacy was evaluated in relation to the baseline serum 25(OH)D level.Results:A total of 2164 patients were randomized to alendronate plus alfacalcidol (combination therapy) or alendronate alone (monotherapy). Although the overall difference in the incidence of vertebral fracture between the two groups was not significant, the combination therapy group had a significantly reduced risk of vertebral fractures after the first 6 months (HR, 0.53). In subgroup analyses, the combination therapy group was superior in the strata of number of prevalent vertebral fractures of ≥2 (HR, 0.51) and grade 3 of prevalent vertebral fractures (HR, 0.55). The rate of non-vertebral weight-bearing bone fractures was significantly lower in the combination therapy group than in the monotherapy group during the follow-up period (HR, 0.31). A lower baseline 25(OH)D level was associated with a higher incidence of non-vertebral weight-bearing bone fractures (HR, 3.42) despite alendronate use. Although one patient given the combination therapy had mild hypercalcemia, serious hypercalcemia and unknown adverse events were not encountered. Because of the limitations presented in this study, these results may not apply to female patients with longer than 2 years of treatments, and to male osteoporosis patients.Conclusions:The combination therapy was no more effective for overall vertebral fracture prevention. However, subgroup analysis has shown that it was more effective for fracture prevention in patients with severe vertebral deformity, multiple prevalent vertebral fractures, and for non-vertebral weight-bearing bone fracture prevention. [ABSTRACT FROM AUTHOR]

Abstract??As inhibitors of bone resorption, bisphosphonates and vitamin D derivatives have been extensively used for the treatment of osteoporosis in various parts of the world, but the clinical effects of these two groups of agents have rarely been compared in detail. A multicenter, prospective, double-blind controlled study was started comparing the effects of etidronate and alfacalcidol (1-alpha-hydroxycholecalciferol) in 414 patients with established osteoporosis from 36 centers. Among these patients, 135 were given 400?mg etidronate daily at bedtime for 2 weeks followed by 10 weeks off treatment, and this cycle was repeated four times along with a placebo indistinguishable from the alfacalcidol capsule daily throughout the 48 weeks of study (Group A, High Dose Etidronate Group). In 133 patients, 200?mg etidronate was used instead of 400?mg (Group B, Low Dose Etidronate Group). In 138 patients, 1??g alfacalcidol was given daily throughout the 48-week study period along with a placebo indistinguishable from the etidronate tablet in four separate periods of 2 weeks (Group C, Control Group). Dual-energy X-ray absorptiometry of the lumbar spine (L2?L4) was performed before the beginning of the study and every 12 weeks thereafter. Changes in spinal deformity were also assessed based on the lateral thoracic and lumbar spine X-ray films taken before and after the study. The lumbar spine bone mineral density (BMD) changes were +3.4% ? 0.6% (mean ? SEM) in Group A, +2.4% ? 0.5% in Group B, and ?0.5% ? 0.4% in Group C, the former two being significantly higher than the last. New occurrence of spinal compression fracture was also significantly reduced in Group A compared to Group C. In patients without previous fracture at entry, incident fracture was 10.2% in Group C, but 0% in Groups A and B. In patients with prevalent fracture at entry, corresponding figures were 21.5% (Group C), 12.0% (Group A), and 13.2% (Group B), respectively. Alfacalcidol maintained lumbar spine BMD, preventing a decrease for 48 weeks, and etidronate significantly increased it further, demonstrating its usefulness in the treatment of established osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Deteriorated quality of life (QOL) is a major problem in osteoporotic women. However, little is known regarding the determinants of QOL in patients with osteoporosis. Objective: Our aim was to explore the role of vitamin D status on QOL score in osteoporosis with high fracture risk. Methods: Patients were osteoporotic women aged ≥70 years and with ≥1 risk factor for incident fracture, namely prevalent osteoporotic fracture, bone mineral density (BMD) >–3.0 SD of young adult mean, or high bone turnover marker. Health-related QOL was assessed using the Japanese Osteoporosis Quality of Life Questionnaire (JOQOL). When patients were classified into quartiles by total QOL score). Serum 25-hydroxyvitamin D (25[OH]D) level was measured by immunoassay. Results: A total of 1585 osteoporotic women were included in the study (age range, 70–95 years). Age, body mass index, serum 25(OH)D status (low, normal, or high), bone mineral density, number of prevalent vertebral fractures, presence of hypertension, presence of osteoarthritis, and history of falls were significantly correlated with QOL quartile. Multivariate liner regression analysis indicated that low serum 25(OH)D level (<20 ng/mL) was an independent determinant of total QOL score quartile (P = 0.0055). The conventional determinants of QOL—age (P < 0.0001), body mass index (P = 0.0060), number of prevalent vertebral fractures (P < 0.0001), presence of osteoarthritis (P = 0.0074), and history of fall (P = 0.0098)—were also independent determinants of total QOL score. Conclusions: These results strongly suggest that low serum 25(OH)D level was a significant determinant of QOL in these osteoporotic women, independently of the conventional factors that reduce QOL. Maintenance of serum 25(OH)D levels >20 ng/mL may be required to maintain patients’ QOL in osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Alendronate, a potent antiresorptive agent, effectively reduces fracture risk. Alendronate increases bone mineral density (BMD) and decreases bone turnover markers to a similar extent in white and Asian people, including Japanese. However, no large trials of this drug have been conducted specifically in the Japanese population.Objective: This study examined the antifracture efficacy of alendronate in Japanese patients.Methods: We conducted a 2-year, multicenter, randomized, double-blind, active-controlled, double-dummy trial of women and men with osteoporosis in Japan, with radiographically diagnosed vertebral fracture being the primary end point. Patients were randomized to receive alendronate 5 mg/d or alfacalcidol 1 gmg/d.Results: A total of 365 patients (349 women, 16 men; mean age, 73 years) were enrolled in the study. At the end of 24 months, spinal BMD was significantly increased versus baseline by a mean of 6.9% in the alendronate-treated group (P < 0.001) and 1.5% in the alfacalcidol-treated group; the median increases in BMD at 24 months versus baseline were 8.3% and 1.4%, respectively. The incidence of vertebral fracture >6 months after randomization (the primary end point) was significantly reduced by 66% (relative risk [RR], 0.34; 95% CI, 0.15–0.74) in the alendronate group (4.3% vs 12.7% incidence). When all fractures during the 24 months were considered, the incidence of multiple (≥2) vertebral fractures also was reduced significantly by 67% (RR, 0.33; 95% CI, 0.11–0.96; 2.4% vs 7.3% incidence). The difference in overall incidence (≥1 vertebral fracture during all 24 months) was not significant (12.2% vs 16.7%), implying that risk reductions (relative to the active control) improved after 6 months. This is consistent with bone biology theory, which predicts that several months are required to refill existing resorption sites and increase bone strength more than the active control. Thus, theory predicts that several months would be required to increase bone strength and reduce fracture risk relative to the active control. This study was limited to Japanese participants, but the findings are consistent with results reported from similar studies among white people. Furthermore, because this was an active-controlled trial, it may have underestimated the antifracture efficacy of alendronate relative to a true placebo.Conclusions: The effectiveness of alendronate in reducing the risk of radiographically defined vertebral fracture in Japanese women and men with osteoporosis is similar to that reported previously in white people. As a consequence, the benefits of alendronate in reducing vertebral and hip fractures can be expected to be substantial and early (beginning at month 6). [Copyright &y& Elsevier]