Risedronate Reduces the Risk of First Vertebral Fracture in Osteoporotic Women

Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined. We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score =–3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg (n= 328) or placebo (n= 312) daily for up to 3 years; all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4% in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval 37% to 90%; P= 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of 70%, 95% CI 8% to 90%; P= 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96%; P= 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women with osteoporosis, with a similar magnitude of effect early and late after the menopause. Received: 12 September 2001 / Accepted: 11 December 2001     

Tolerability of risedronate in postmenopausal women intolerant of alendronate

Bisphosphonates are effective treatments for osteoporosis, but some have been associated with upper gastrointestinal intolerance. This randomized, double-blind study assessed the upper gastrointestinal tolerability of risedronate in postmenopausal women who had discontinued alendronate treatment because of upper gastrointestinal adverse events. Sixty-six women who had previously discontinued treatment with alendronate 10 mg/day because of upper gastrointestinal symptoms received placebo (N=31) or risedronate 5 mg (N=35) daily for 3 months. The primary outcome was the rate of discontinuation due to upper gastrointestinal adverse events: 5/31 (16.1%) in the placebo group, and 4/35 (11.4%) in the risedronate group. Discontinuation rates were also similar in the two treatment groups among subgroups of patients with a history of gastrointestinal disorder, prior use of acid suppression drugs, and concomitant use of NSAIDs. The overall incidence of upper gastrointestinal events was comparable between the placebo (19.4%) and risedronate (20.0%) groups. Overall, risedronate 5 mg/day for 3 months was as well tolerated as placebo in patients who could not tolerate alendronate 10 mg. These results are consistent with, and complement those from previous studies showing that risedronate 5 mg has a gastrointestinal tolerability similar to that of placebo.     

Systemic hematologic effects of PEG-rHuMGDF-induced megakaryocyte hyperplasia in mice

PEG-rHuMGDF injected daily in normal mice causes a rapid dose-dependent increase in megakaryocytes and platelets. At the same time that platelet numbers are increased, the mean platelet volume (MPV) and platelet distribution width (PDW) can be either decreased, normal, or increased depending on the dose and time after administration. Thus, PEG-rHuMGDF at a low dose causes decreases in MPV and PDW, MGDF at an intermediate dose causes an initial increase followed by a decrease in MPV and PDW, and PEG-rHuMGDF at higher doses causes an increase in MPV and PDW followed by a gradual normalization of these platelet indices. In addition to the expected thrombocytosis after 7 to 10 days of daily injection of high doses of PEG-rHuMGDF, a transient decrease in peripheral red blood cell numbers and hemoglobin is noted accompanied in the bone marrow by megakaryocytic hyperplasia, myeloid hyperplasia, erythroid and lymphoid hypoplasia, and deposition of a fine network of reticulin fibers. Splenomegaly, an increase in splenic megakaryocytes, and extramedullary hematopoiesis accompany the hematologic changes in the peripheral blood and marrow to complete a spectrum of pathologic features similar to those reported in patients with myelofibrosis and megakaryocyte hyperplasia. However, all the PEG-rHuMGDF-initiated hematopathology including the increase in marrow reticulin is completely and rapidly reversible upon the cessation of administration of PEG-rHuMGDF. Thus, transient hyperplastic proliferation of megakaryocytes does not cause irreversible tissue injury. Furthermore, PEG-rHuMGDF completely ameliorates carboplatin-induced thrombocytopenia at a low-dose that does not cause the hematopathology associated with myelofibrosis.     

A Novel Monthly Dosing Regimen of Risedronate for the Treatment of Postmenopausal Osteoporosis: 2-Year Data

This 2-year trial evaluated the efficacy and tolerability of a monthly oral regimen of risedronate. Postmenopausal women with osteoporosis were randomly assigned to double-blind treatment with risedronate 75 mg on 2 consecutive days each month (2CDM) or 5 mg daily. The primary end point was the percentage change from baseline in lumbar spine bone mineral density (BMD) at 12 months. Secondary end points included the change in BMD of the lumbar spine and proximal femur and in bone turnover markers as well as the number of subjects with at least one new vertebral fracture over 24 months. Among 1,229 patients who were randomized and received at least one dose of risedronate, lumbar spine BMD was increased in both treatment groups: mean percentage change from baseline was 4.2 ± 0.19 and 4.3 ± 0.19 % in the 75 mg 2CDM and 5 mg daily groups, respectively, at month 24. The treatment difference was 0.17 (95 % confidence interval ?0.35 to 0.68). There were no statistically significant differences between treatment groups on any secondary efficacy parameters. Both treatment regimens were well tolerated. Risedronate 75 mg 2CDM was noninferior in BMD efficacy and did not show a difference in tolerability compared to 5 mg daily after 24 months of treatment in women with postmenopausal osteoporosis. This monthly regimen may provide a more convenient dosing schedule to some patients with postmenopausal osteoporosis.     

Video Modeling and Video Feedback to Reduce Time to Perform Intravenous Cannulation in Medical Students: A Randomized-Controlled Mixed-Methods Study

Combined video modeling (VM) and video feedback (VF) may be more beneficial than traditional feedback when teaching procedural skills. This study examined whether repeated VM and VF compared with VM alone reduced the time required for medical students to perform peripheral intravenous (IV) cannulation. Twenty-five novice medical students were randomly assigned to groups in a one-way blinded embedded mixed-methods study to perform IV cannulation. Participants received standardized instruction and performed IV cannulation on each other while being audio-video recorded. They were assigned to review a video of an expert performing IV cannulation (VM alone), or both the expert video and a video of their own most recent IV cannulation (VM+VF), before returning to perform another IV cannulation. This was repeated for a total of four IV cannulation encounters and three video reviews. A post-test interview was also conducted and analyzed qualitatively using thematic content analysis. The median [interquartile range] time required to perform IV cannulation in the final encounter was significantly different between the VM+VF group vs VM alone group (126 [93-226] sec vs 345 [131-537] sec, respectively; median difference, 111 sec; 95% confidence interval, 8 to 391; P = 0.02). There was no significant difference in IV cannulation success between VM alone and VM+VF in the final encounter (75% vs 85% respectively; P = 0.65). For the VM+VF group, the time to perform IV cannulation was reduced after the final encounter compared with the baseline encounter (P = 0.002), which was not true of the VM alone group (P = 0.35). Video modeling and feedback shortened time to IV skill completion, reduced complications, and improved satisfaction in novice medical students.     

Characterizing microarchitectural changes at the distal radius and tibia in postmenopausal women using HR-pQCT

Summary

Limited prospective evidence exists regarding bone microarchitectural deterioration. We report annual changes in trabecular and cortical bone microarchitecture at the distal radius and tibia in postmenopausal women. Lost trabeculae with corresponding increase in trabecular thickness at the radius and thinning tibial cortex indicated trabecularization of the cortex at both sites.

Introduction

Osteoporosis is characterized by low bone mass and the deterioration of bone microarchitecture. However, limited prospective evidence exists regarding bone microarchitectural changes in postmenopausal women: a population prone to sustaining osteoporotic fractures. Our primary objective was to characterize the annual change in bone area, density, and microarchitecture at the distal radius and distal tibia in postmenopausal women.

Methods

Distal radius and tibia were measured using high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and 1 year later in 51 women (mean age?±?SD, 77?±?7 years) randomly sampled from the Saskatoon cohort of the Canadian Multicentre Osteoporosis Study (CaMos). We used repeated measures analysis of variance (ANOVA) with Bonferroni adjustment for multiple comparisons to characterize the mean annual change in total density, cortical perimeter, trabecular and cortical bone area, density, content, and microarchitecture. Significant changes were accepted at P?<?0.05.

Results

At the distal radius in women without bone-altering drugs, total density (?1.7 %) and trabecular number (?6.4 %) decreased, while trabecular thickness (+6.0 %), separation (+8.6 %), and heterogeneity (+12.1 %) increased. At their distal tibia, cortical area (?4.5 %), density (?1.9 %), content (?6.3 %), and thickness (?4.4 %) decreased, while trabecular area (+0.4 %) increased.

Conclusions

The observed loss of trabeculae with concomitant increase in trabecular size at the distal radius and the declined cortical thickness, density, and content at the distal tibia indicated a site-specific trabecularization of the cortical bone in postmenopausal women.