Showing papers by "David J. Hosking published in 2005"

Comparison of a Single Infusion of Zoledronic Acid with Risedronate for Paget's Disease

Abstract: Background The advent of bisphosphonates advanced therapy for Paget's disease, but more effective and convenient agents are needed to increase adherence. Zoledronic acid, a bisphosphonate administered as a single intravenous infusion, might meet these needs. Methods In two identical, randomized, double-blind, actively controlled trials of 6 months' duration, we compared one 15-minute infusion of 5 mg of zoledronic acid with 60 days of oral risedronate (30 mg per day). The primary efficacy end point was the rate of therapeutic response at six months, defined as a normalization of alkaline phosphatase levels or a reduction of at least 75 percent in the total alkaline phosphatase excess. The results of the studies were pooled. Results At six months, 96.0 percent of patients receiving zoledronic acid had a therapeutic response (169 of 176), as compared with 74.3 percent of patients receiving risedronate (127 of 171, P<0.001). Alkaline phosphatase levels normalized in 88.6 percent of patients in the zoledronic...

Reduced bone mineral density in male renal transplant recipients: evidence for persisting hyperparathyroidism.

Abstract: Background: Osteoporosis is increasingly recognized as a major source of morbidity following renal transplantation. The aim of this cross-sectional study was to determine the prevalence of osteoporosis in a cohort of male transplant recipients and examine factors that may influence their bone loss. Methods: Bone mineral density (BMD) and biochemical markers of bone metabolism were measured in 134 out of 154 male renal allograft recipients in our center. Results: The mean age of the patients was 49.7 years (range 26–76) with a median of 6 years post-transplant. Only 17% had normal BMD, 30% were osteoporotic at either hip or spine, and this proportion rose to 41% if the ultradistal radius was included. Parathyroid hormone (PTH) was negatively correlated with BMD at all skeletal sites. In a multiple regression model, independent predictors of femoral neck BMD included body mass index (p=0.004), diabetes (p=0.025), and PTH (p=0.049). The only independent predictor of BMD at the ultradistal radius was PTH (p<0.001). Nineteen men sustained a total of 25 appendicular fractures after transplantation (median time to fracture was 3 years). Prevalent vertebral fractures were only identified in five men. PTH was elevated in 72.4% of patients (mean PTH 142 ± 118 pg/ml). Bone resorption markers were increased in 48% of patients. PTH was positively correlated with serum carboxyterminal telopeptide of type 1 collagen (r=0.473, p<0.001) and procollagen type 1 amino terminal propeptide (r=0.419, p<0.001). Conclusions: Osteopenia and osteoporosis are common in male transplant recipients, and the hip and radius are the most severely affected sites. Elevated rates of bone resorption driven by hyperparathyroidism appear to be the most important contributing factor.

Osteoporosis therapy: an example of putting evidence-based medicine into clinical practice.

Abstract: A major aim of evidence-based medicine is to assist clinical decision-making by providing the most current and reliable medical information. Systematic reviews and meta-analyses are important tools in this process. Systematic reviews identify and compile relevant evidence, while meta-analyses summarize and quantify the results of such reviews. Results from meta-analyses are, at present, the main source of summary evidence for the efficacy of treatments for a specific condition. They are important tools for helping to choose among treatment options, although they cannot be used to directly compare the magnitude of the effect of various therapies. However, the methods used and the consequent clinical value of the results, may be poorly understood by clinicians, who may therefore not take full advantage of the evidence. Recently, a panel of experts in osteoporosis and evidence-based medicine applied rigorous, validated, scientific standards to produce a systematic review and meta-analysis of randomized controlled trials of anti-resorptive agents used to treat osteoporosis. They found that, although several agents reduced the risk of vertebral fracture, only two, alendronate and risedronate, demonstrated convincing evidence for both non-vertebral and vertebral fracture risk reductions. The clinical implication of these results is that there are important differences in anti-fracture efficacy among currently available agents. In the absence of evidence from head-to-head clinical trials and because of the systematic nature and methodological rigor of the analyses, these data provide important information for clinical decision-making.

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.