Showing papers by "David J. Hosking published in 2004"

Ten years' experience with alendronate for osteoporosis in postmenopausal women.

Abstract: Background: Antiresorptive agents are widely used to treat osteoporosis. We report the results of a multinational randomized, double-blind study, in which postmenopausal women with osteoporosis were treated with alendronate for up to 10 years. Methods: The initial three-year phase of the study compared three daily doses of alendronate with placebo. Women in the original placebo group received alendronate in years 4 and 5 and then were discharged. Women in the original active-treatment groups continued to receive alendronate during the initial extension (years 4 and 5). In two further extensions (years 6 and 7, and 8 through 10), women who had received 5 mg or 10 mg of alendronate daily continued on the same treatment. Women in the discontinuation group received 20 mg of alendronate daily for two years and 5 mg daily in years 3, 4, and 5, followed by five years of placebo. Randomized group assignments and blinding were maintained throughout the 10 years. We report results for the 247 women who participated in all four phases of the study. Results: Treatment with 10 mg of alendronate daily for 10 years produced mean increases in bone mineral density of 13.7 percent at the lumbar spine (95 percent confidence interval, 12.0 to 15.5 percent), 10.3 percent at the trochanter (95 percent confidence interval, 8.1 to 12.4 percent), 5.4 percent at the femoral neck (95 percent confidence interval, 3.5 to 7.4 percent), and 6.7 percent at the total proximal femur (95 percent confidence interval, 4.4 to 9.1 percent) as compared with base-line values; smaller gains occurred in the group given 5 mg daily. The discontinuation of alendronate resulted in a gradual loss of effect, as measured by bone density and biochemical markers of bone remodeling. Safety data, including fractures and stature, did not suggest that prolonged treatment resulted in any loss of benefit. Conclusions: The therapeutic effects of alendronate were sustained, and the drug was well tolerated over a 10-year period. The discontinuation of alendronate resulted in the gradual loss of its effects.

Ten Years’ Experience With Alendronate for Osteoporosis in Postmenopausal Women

Abstract: This multinational randomized double-blind trial, the Alendronate Phase III Osteoporosis Treatment Study, examined the results of alendronate therapy in postmenopausal women with osteoporosis who now have been followed for 10 years. A total of 227 women completed all phases of the study. Those participating were assigned to receive 5 or 10 mg of alendronate orally or placebo each day. The primary end point was the change in bone mineral density (BMD) in the lumbar spine. BMD also was measured at the femoral neck, trochanter, total proximal femur, forearm region, and the total body. From 17% to 31% of women in the various treatment groups had preexisting vertebral fractures. BMD continued to increase in the later years of the study in women given 5 or 10 mg of alendronate daily. The mean cumulative increase after 10 years in women taking 10 mg daily was 13.7%. Markers of bone remodeling (urinary N-telopeptides of type I collagen, bone-specific alkaline phosphatase) decreased, and this effect continued through 10 years of treatment. These markers increased within a year after alendronate was discontinued, although mean levels remained below baseline. There were no significant group differences in new vertebral fractures. The 3 groups also had similar safety profiles in the last 3 years of the study. No deaths were ascribed to alendronate therapy. Alendronate therapy continued to be effective over 10 years in these postmenopausal women, as estimated by both BMD measurements and effects on bone remodeling. The antifracture effect of alendronate did not appear to decrease over time.

A randomised, controlled comparison of different calcium and vitamin D supplementation regimens in elderly women after hip fracture: The Nottingham Neck of Femur (NONOF) Study

Abstract: BACKGROUND: survivors of hip fracture are at 5- to 10-fold risk of a second hip fracture. There is little consensus about secondary prevention. Many are given calcium and vitamin D, but the evidence supporting this is circumstantial. OBJECTIVE: to compare the effects of different calcium and vitamin D supplementation regimens on bone biochemical markers, bone mineral density and rate of falls in elderly women post-hip fracture. DESIGN: randomised controlled trial. SETTING: orthogeriatric rehabilitation ward. METHODS: 150 previously independent elderly women, recruited following surgery for hip fracture, were assigned to receive a single injection of 300,000 units of vitamin D(2), injected vitamin D(2) plus 1 g/day oral calcium, 800 units/day oral vitamin D(3) plus 1 g/day calcium, or no treatment. Follow-up was one year, with measurement of 25-hydroxyvitamin D, parathyroid hormone, bone mineral density, and falls. RESULTS: mean 25-hydroxyvitamin D increased and mean parathyroid hormone was suppressed in all the actively treated groups, more so in the group receiving combined oral vitamin D and calcium. Twenty per cent of participants injected with vitamin D were deficient in 25-hydroxyvitamin D a year later. Bone mineral density showed small but statistically significant differences of up to 4.6% between actively treated groups and placebo. Relative risk of falling in the groups supplemented with vitamin D was 0.48 (95% CI 0.26-0.90) compared with controls. CONCLUSION: Vitamin D supplementation, either orally or with injected vitamin D, suppresses parathyroid hormone, increases bone mineral density and reduces falls. Effects may be more marked with calcium co-supplementation. The 300,000 units of injected vitamin D may not last a whole year. Language: en

Changes in bone density and turnover after alendronate or estrogen withdrawal.

Abstract: OBJECTIVE To compare bone mineral density (BMD) and bone turnover changes after therapy withdrawal in postmenopausal women treated with alendronate or estrogen-progestin. DESIGN In this randomized, blinded, multinational, placebo-controlled trial, 1,609 healthy postmenopausal women ages 45 to 59 years were assigned to receive alendronate, placebo, or open-label estrogen-progestin (conjugated equine estrogens plus medroxyprogesterone acetate or a cyclic regimen of 17 beta-estradiol, norethisterone acetate and estradiol). Of the original women, one third after year 2 and one third after year 4 were switched from alendronate to placebo, while remaining blinded to treatment assignment. The women taking estrogen-progestin in years 1 to 4 were followed off therapy in years 5 and 6. BMD at the lumbar spine and hip and biochemical markers of bone turnover were measured. RESULTS The treatment groups described in the current report represent 860 women at baseline; 481 women entered year 5, and 430 completed 6 years. BMD steadily decreased in the placebo group during all 6 years. In contrast, spine and hip BMD increased during the first 4 years in the groups receiving daily continuous alendronate 5 mg and estrogen-progestin. During years 5 and 6, BMD decreased at the lumbar spine -2.42% (95% CI = -4.10, -0.74) and total hip -1.09% (-2.60, 0.41) in the group previously treated with alendronate 5 mg for 4 years. In comparison, large BMD decreases were observed at the spine [-7.69% (-8.96, -6.41)] and total hip [-5.16% (-6.30, -4.01)] among women who had received estrogen-progestin for 4 years. CONCLUSION Alendronate produces greater residual skeletal effects than estrogen-progestin after therapy discontinuation.

Prevention of Postmenopausal Bone Loss: Six-Year Results from the Early Postmenopausal Intervention Cohort Study

Abstract: We report the effect of continuous treatment with alendronate for 6 yr vs. placebo in the Early Postmenopausal Intervention Cohort study. A total of 1609 healthy, early postmenopausal women were recruited; we describe results for the 585 women who received continuous placebo or alendronate (2.5 or 5 mg) daily for 6 yr. Bone mineral density (BMD) was evaluated at the lumbar spine, hip, forearm, and total body at baseline and annually thereafter. Bone turnover markers were measured every 6 months from baseline to yr 2 and annually thereafter. Adverse experiences, including upper gastrointestinal events and fractures, were recorded throughout the study. Women receiving placebo experienced progressive decreases in BMD at all skeletal sites. Patients receiving alendronate experienced significant gains in spine and hip BMD that were maintained through yr 6. Significantly greater, dose-related decreases in bone turnover markers in the alendronate groups vs. placebo occurred within the first year and were sustained through yr 6. Women receiving alendronate had adverse experience incidences similar to those receiving placebo. Fractures occurred in 11.5, 10.3, and 8.9% of women taking placebo, 2.5 mg alendronate, or 5 mg alendronate daily, respectively. Therapy with alendronate is an effective and promising strategy for the prevention of postmenopausal osteoporosis.

Putting evidence-based medicine into clinical practice: comparing anti-resorptive agents for the treatment of osteoporosis.

Abstract: SUMMARYObjective: To compare the effectiveness of anti-resorptive agents in reducing the risk of vertebral and non-vertebral fractures using data from published meta-analyses and the technique of adjusted indirect comparisons.Research design and methods: Pairs of agents were compared by adjusted indirect comparison of their effects relative to a common comparator (placebo) using meta-analyses published by The Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group.Results: Adjusted indirect comparisons identified only one pair of agents that had significantly different effects on vertebral fracture incidence: alendronate was 34% more effective than calcitonin (Relative Risk: 0.66, 95% Confidence Interval: 0.48–0.90). Alendronate was significantly more effective than risedronate, calcitonin, estrogen, etidronate, and raloxifene (Relative Risks: 0.70 [0.49, 0.99], 0.64 [0.42, 0.98], 0.59 [0.41, 0.84], 0.52 [0.32, 0.82], and 0.56 [0.40, 0.78], respectively) in reducing the incidence of no...

Longitudinal changes of insulin-like growth factors and their binding proteins throughout normal pregnancy

Abstract: Background Insulin-like growth factors (IGFs) are anabolic proteins that are essential regulators of cell division, differentiation and growth. We describe the longitudinal changes in IGF-I, IGF-II and the binding proteins IGFBP-1, -2 and -3 before and during normal pregnancy. Method Serum samples were taken before conception and then at 12, 24 and 36 weeks of gestation in 41 healthy women with uncomplicated pregnancies. We measured IGF-I using an automated chemiluminescent method, IGF-II and IGFBP-2 using in-house radioimmunoassays (RIAs), and IGFBP-1 and IGFBP-3 using commercial enzyme-linked immunosorbent assay (ELISA) and RIA kits, respectively. Because of the potential haemodilution effects during pregnancy, albumin was also measured in all samples. Results There was a significant fall in IGF-I during the first (36%) and second trimesters (21%) followed by an increase of 25% at 36 weeks. During pregnancy, the mean IGF-II concentrations fell by 12% at 12 weeks, 8% at 24 and 8% at 36 weeks compared with pre-conception values. When IGF-II results were adjusted for the haemodilution of pregnancy, its concentrations increased. During pregnancy, there was a rapid increase in mean IGFBP-1 levels by 17-fold (12 weeks), 24-fold (24 weeks) and 25-fold (36 weeks). IGFBP-2 concentrations fell after conception but started to increase towards term. This increase was more significant when adjusted for haemodilution. In contrast, IGFBP-3 concentrations increased significantly throughout pregnancy. Conclusion Our data on the physiological changes of IGFs and their binding proteins add further evidence of the vital roles of these hormones throughout normal pregnancy.

Putting evidence-based medicine into clinical practice: comparing anti-resorptive agents for the treatment of

Abstract: (Relative Risks: 0.70 [0.49, 0.99], 0.64 [0.42, 0.98], 0.59 [0.41, 0.84], 0.52 [0.32, 0.82], and 0.56 [0.40, 0.78], respectively) in reducing the incidence of non-vertebral fractures. No other significant pairwise differences were observed. Conclusions: The results suggest that there are differences in anti-fracture efficacy among antiresorptive agents, particularly for non-vertebral fractures. Direct head-to-head comparisons would be needed to confirm these findings but are unlikely to be conducted. SUMMARY

Oral antiresorptive therapy.

Abstract: Oral antiresorptive agents play a pivotal role in the management of osteoporosis. This paper discusses the effects and potential future role of newer agents such as ibandronate. Alternative dosing schedules and routes of administration have become available and may improve fracture protection, compliance, and tolerability for the long term treatment of a chronic condition such as osteoporosis. Increasingly these agents are being used to reduce bone loss in other diseases associated with high risk for osteoporosis such as organ transplantation and cystic fibrosis. Such studies may act as prototypes for the extended use of this class of drugs in other chronic inflammatory disease states. The innovative, yet disappointing results from combining an antiresorptive agent (alendronate) with the anabolic effects of teriparatide is also discussed. The major problem that remains is the lack of direct comparison between the agents in terms of fracture endpoints.