A 3-year prospective, randomized, placebo-controlled trial of oral clodronate 800 mg showed that the incidence of clinical fractures was decreased by 20% in 5596 elderly women unselected for osteoporosis. The effect occurred in the absence of systematic calcium and vitamin D supplementation and was observed across a wide range of BMDs.Introduction: To date, most studies with bisphosphonates have reported on their use in individuals selected to be at high risk for fracture usually by the presence of low BMD or a prior fragility fracture, usually of the spine. We wished to determine the effect of the bisphosphonate, clodronate, on the rate of fractures in women Ն75 years of age living in the community. Materials and Methods: Women Ն75 years of age living in the general community in South Yorkshire and North Derbyshire, identified from general practice registers, were recruited by letter of invitation to a randomized, double-blind, controlled trial of 800 mg oral clodronate (Bonefos) or matching placebo daily over 3 years. The main outcomes were the incidences of hip and any clinical fracture. Results: Of the 5579 elderly women included in the intention-to-treat analysis of efficacy, 114 had a new hip fracture during the 3-year treatment phase: 56 (2.0%) women in the clodronate group and 58 (2.1%) women in the placebo group (hazard ration [HR], 1.02; 95% CI, 0.71-1.47). Clodronate did, however, decrease the incidence of any clinical fracture by 20% (264 women [9.5%] versus 337 [12.1%] in the placebo group; HR, 0.80; 95% CI, 0.68-0.94). The incidence of osteoporosis-associated nonhip fractures was also significantly decreased by 29% (5.2% versus 7.4%; HR, 0.71; 95% CI, 0.57-0.87). The ability of clodronate to reduce the risk of osteoporotic fracture was independent of baseline BMD, but the number needed-to-treat was lower in the presence of osteoporosis. Conclusions: Oral daily clodronate can prevent fractures without significant adverse effects in elderly women living in the general community. The effect on hip fracture risk is not significant, but an effect similar to that at other nonvertebral sites cannot be excluded. This study suggests that antiresorptive therapies can reduce fracture incidence in high-risk individuals even in the presence of a normal or osteopenic BMD.
Immediately after hemodialysis, the urea concentration rebounds upwards as urea continues to be transferred into the arterial circulation from peripheral body compartments. This rebound takes at least 30 minutes to complete. Hemodialysis is quantified as the Kt/V, calculated prom pre- and post-dialysis urea samples. Unless the post-dialysis sample is taken at least 30 minutes after dialysis, the Kt/V will be overestimated. This overestimation will be relatively greater in short high-efficiency dialyses, which have greater post-dialysis rebounds. We propose a method of correction that uses only the conventional pre- and immediate post-dialysis samples and is based on the physiologically-appropriate patient clearance time (tp). This is the time needed to clear all body compartments when the dialyzer clearance is infinite. The tp can be calculated from the pre-, immediate post- and 30-minute post-dialysis urea concentrations and was 35 minutes (SD 16) in 29 patients undergoing short (149 min) hemodiafiltration and standard (243 min) hemodialysis the following week. There was no significant difference between tp values calculated during the two treatments. Standard Kt/V can be corrected by multiplying by t/(t + tp) and dialysis time should be increased by tp x Kt/V minutes to compensate for the rebound. Despite individual variations in tp, a value of tp = 35 was sufficient to correct Kt/V in all patients. Kt/V corrected in this way agreed with Kt/V calculated using a 60-minute post-dialysis sample (r = 0.856, P < 0.001). The method predicted the 60-minute post-rebound concentration (SE 0.5 mM, r = 0.983, P < 0.001) and the addition of 35 minutes to the treatment time corrected for the rebound in both conventional and short treatments. Similar simple equations corrected the error in V caused by rebound effects.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.