Biomedical subjects

Nicole Zytaruk

Publications and source records attributed to Nicole Zytaruk.

9 recordsLinked to original sources

PubMed2006

Parathyroid hormone for the treatment of osteoporosis: a systematic review.

BACKGROUND: Human parathyroid hormone (hPTH)(1-34) was approved in 2004 for the treatment of severe osteoporosis. Members of the Osteoporosis Canada clinical guidelines committee conducted a systematic review of randomized controlled trials (RCTs) to assess the efficacy and safety of hPTH for fracture prevention in postmenopausal women and men with osteoporosis. METHODS: We searched MEDLINE, EMBASE, HTA, Current Contents and the Cochrane Controlled Trials Registry for published data from 1966 to February 2005. A systematic literature search for RCTs was conducted using the Cochrane Collaborative approach. We identified 12 trials that randomly assigned patients either to hPTH or placebo or to hPTH or an active comparator and were at least 1 year in duration. Outcomes included change in bone mineral density (BMD), fractures, back pain and adverse events. Two independent reviewers abstracted data on study characteristics and outcomes. RESULTS: hPTH(1-34) significantly increases lumbar spine BMD, with smaller increases at the femoral neck and total hip. hPTH(1-84) significantly increases lumbar spine BMD. The data show a significant reduction in both vertebral and nonvertebral fractures with hPTH(1-34) in postmenopausal women with previous vertebral fractures. There were no data on fractures comparing the approved dose of hPTH(1-34) with active comparators. INTERPRETATION: There is Level I evidence that hPTH(1-34) significantly increases BMD at all skeletal sites except the radius and significantly reduces the risk of new vertebral and nonvertebral fractures in postmenopausal women with prior fractures.

Adrenal Cortex Hormones↗

PubMed2005

Do hip protectors decrease the risk of hip fracture in institutional and community-dwelling elderly? A systematic review and meta-analysis of randomized controlled trials.

Hip fractures are an important cause of morbidity and mortality in the elderly. Hip protectors are padded undergarments designed to decrease the impact of a fall on the hip. We systematically reviewed randomized controlled trials of hip protectors to determine if they reduce hip fractures in the elderly. Analyses were pooled according to participant residence--community or institutional (the latter, included nursing homes, residential group homes or seniors' hostels). We included individually randomized and statistically adjusted cluster randomized trials. Seven trials of 12- to 28-month duration were included. The Safehip brand of hip protector was used in most studies. Compliance rates in the treatment groups varied from 31 to 68%. In four trials including a total of 5,696 community-dwelling seniors, the hip fracture rates in control groups ranged from 1.1 to 7.4%, and the pooled risk difference with hip protector allocation was 0% [95% confidence intervals (CI), -1%, +1%), with a relative risk of 1.07 (0.81, 1.42). In three trials including 1,188 institutionalized elderly participants, hip fracture rates in the control groups varied from 8 to 19.4%, and the pooled risk difference for sustaining one or more hip fractures with hip protector allocation was -3.7% (95% CI, -7.4%, 0.1%), with a relative risk of 0.56 (0.31, 1.01) (with statistically significant heterogeneity of treatment effect). In a post-hoc subgroup analysis of two trials comprised of exclusively nursing home residents, the risk difference with hip protector allocation was -4.4% (-8.09, -0.76) with a relative risk of 0.50 (0.28, 0.91) (n=1,014). Thus, there is little evidence to support the use of hip protectors outside the nursing home setting. The potential benefit of hip protectors in reducing hip fractures in nursing home residents requires further confirmation.

Activities of Daily Living↗

PubMed2002

Meta-analyses of therapies for postmenopausal osteoporosis. II. Meta-analysis of alendronate for the treatment of postmenopausal women.

OBJECTIVE: To review the effect of alendronate on bone density and fractures in postmenopausal women. DATA SOURCE: We searched MEDLINE, EMBASE, Current Contents, and the Cochrane Controlled trials registry from 1980 to 1999, and we examined citations of relevant articles and proceedings of international meetings. STUDY SELECTION: We included 11 trials that randomized women to alendronate or placebo and measured bone density for at least 1 yr. DATA EXTRACTION: For each trial, three independent reviewers assessed the methodological quality and abstracted data. DATA SYNTHESIS: The pooled relative risk (RR) for vertebral fractures in patients given 5 mg or more of alendronate was 0.52 [95% confidence interval (CI), 0.43-0.65]. The RR of nonvertebral fractures in patients given 10 mg or more of alendronate was 0.51 (95% CI 0.38-0.69), an appreciably greater effect than for the 5 mg dose. We found a similar reduction in RR across nonvertebral fracture types; in particular, RR reductions for fractures traditionally thought to be "osteoporotic," such as hip and forearm, were very similar to RR reductions for "nonosteoporotic" fractures. Individual studies showed similar results, reflected in the P values of the test of heterogeneity (P = 0.99 for vertebral and 0.88 for nonvertebral fractures). Alendronate produced positive effects on the percentage change in bone density, which increased with both dose and time. After 3 yr of treatment with 10 mg of alendronate or more, the pooled estimate of the difference in percentage change between alendronate and placebo was 7.48% (95% CI 6.12-8.85) for the lumbar spine (2-3 yr), 5.60% (95% CI 4.80-6.39) for the hip (3-4 yr), 2.08% (95% CI 1.53-2.63) for the forearm (2-4 yr), and 2.73% (95% CI 2.27-3.20) for the total body (3 yr). Heterogeneity of the treatment effect of alendronate was not consistently explained by any of our a priori hypotheses; in particular, the effect was very similar in prevention and treatment studies. The pooled RR for discontinuing medication due to adverse effects for 5 mg or greater of alendronate was 1.15 (95% CI 0.93-1.42). The pooled RR for discontinuing medication due to gastro-intestinal (GI) side effects for 5 mg or greater was 1.03 (0.81-1.30, P = 0.83), and the pooled RR for GI adverse effects with continuation of medication was 1.03 (0.98 to 1.07) P = 0.23. CONCLUSIONS: Alendronate increases bone density in both early postmenopausal women and those with established osteoporosis while reducing the rate of vertebral fracture over 2-3 yr of treatment. Reductions in nonvertebral fractures are evident among postmenopausal women without prevalent fractures and have bone mineral density (BMD) levels below the World Health Organization threshold for osteoporosis. The impact on fractures appears consistent across all fracture types, casting doubt on traditional distinctions between osteoporotic and nonosteoporotic fractures.

Alendronate↗

PubMed2002

Meta-analyses of therapies for postmenopausal osteoporosis. III. Meta-analysis of risedronate for the treatment of postmenopausal osteoporosis.

OBJECTIVE: To review the effect of risedronate on bone density and fractures in postmenopausal women. DATA SOURCES: We searched MEDLINE from 1966 to the end of 2000 and examined citations of relevant articles and the proceedings of international osteoporosis meetings. STUDY SELECTION: We included eight randomized, placebo-controlled trials of postmenopausal women receiving risedronate or placebo with a follow-up of at least one year and providing data on bone density or fracture rate. DATA EXTRACTION: For each trial, two independent reviewers assessed the methodological quality and abstracted data. DATA SYNTHESIS: The major methodological limitation of the trials was the loss to follow-up, which was over 20% in most trials and over 35% in the largest study. However, the magnitude of the treatment effect was unrelated to loss to follow-up, and in one of the largest trials, more high-risk patients were lost to follow-up in the control than in the treatment group. The pooled relative risk (RR) for vertebral fractures in women given 2.5 mg or more of risedronate was 0.64 [95% confidence interval (CI) 0.54, 0.77]. The pooled RR of nonvertebral fractures in patients given 2.5 mg or more of risedronate was 0.73 (95% CI 0.61, 0.87). Risedronate produced positive effects on the percentage change in bone density of the lumbar spine, combined forearm, and femoral neck that were generally larger with the 5-mg daily dose than with cyclical administration or the 2.5-mg dose. The pooled estimate of the difference in percentage change between 5 mg risedronate and placebo after the final year of treatment (1.5-3 yr) was 4.54% (95% CI 4.12, 4.97) for the lumbar spine, and 2.75% (95% CI 2.32, 3.17) at the femoral neck. CONCLUSIONS: Risedronate substantially reduces the risk of both vertebral and nonvertebral fractures. This fracture reduction is accompanied by an increase in bone density of the lumbar spine and femoral neck in both early postmenopausal women and those with established osteoporosis.

Etidronic Acid↗

PubMed2002

Meta-analyses of therapies for postmenopausal osteoporosis. IV. Meta-analysis of raloxifene for the prevention and treatment of postmenopausal osteoporosis.

OBJECTIVE: To review the effect of raloxifene on bone density and fractures in postmenopausal women. DATA SOURCE: We searched MEDLINE from 1966 to 2000 and examined citations of relevant articles and the proceedings of international osteoporosis meetings. STUDY SELECTION: We included seven trials that randomized women to raloxifene or placebo, with both groups receiving similar calcium and vitamin D supplementation, and measured bone density for at least one year. DATA EXTRACTION: For each trial, three independent reviewers abstracted the data and assessed the methodological quality using a validated tool. DATA SYNTHESIS: Data from one large dominating trial suggest a reduction in vertebral fractures with a relative risk (RR) of 0.60 [95% confidence interval (CI) 0.50-0.70, P < 0.01]. The RR of nonvertebral fractures in patients given 60 mg or more of raloxifene in the larger study was 0.92 (95% CI 0.79-1.07, P = 0.27). Raloxifene resulted in positive effects on the percentage change in bone density, which increased over time and was independent of dose. At the final year, point estimates and 95% CIs for the differences in percent change in bone density (95% CI) between raloxifene and placebo groups were 1.33 (95% CI 0.37-2.30) for total body, 2.51 (95% CI 2.21-2.82) for lumbar spine, 2.05 (95% CI 0.71-3.39) for combined forearm, and 2.11 (95% CI 1.68-2.53) for combined hip (P < 0.01 at all four sites). Results were similar across studies, and formal tests of heterogeneity did not approach conventional statistical significance. Raloxifene slightly increased rates of withdrawal from therapy as a result of adverse effects (RR 1.15, 95% CI 1.00-1.33, P = 0.05). The pooled RR was significant for hot flashes 1.46 (95% CI 1.23-1.74, P < 0.01) and nonsignificant for leg cramps 1.64 (95% CI 0.84-3.20, P = 0.15). CONCLUSION: Raloxifene increases bone density, and the effect increases over 2 yr. The data suggest a positive impact of raloxifene on vertebral fractures. There was little effect of raloxifene on nonvertebral fractures.

Female↗

PubMed2002

Meta-analyses of therapies for postmenopausal osteoporosis. V. Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women.

OBJECTIVE: To review the effect of hormone replacement therapy (HRT) on bone density and fractures in postmenopausal women. DATA SOURCE: We searched MEDLINE and EMBASE from 1966 to 1999, the Cochrane Controlled Register, citations of relevant articles, and proceedings of international meetings for eligible randomized controlled trials. We contacted osteoporosis investigators to identify additional studies, and primary authors for unpublished data. STUDY SELECTION: We included 57 studies that randomized postmenopausal women to HRT or a control (placebo or calcium/vitamin D) and were of at least 1 yr in duration. Seven of these studies reported fractures. DATA ABSTRACTION: For each study, three independent reviewers assessed the methodological quality and abstracted the data. DATA SYNTHESIS: HRT showed a trend toward reduced incidence of vertebral fractures [relative risk (RR) 0.66, 95% confidence interval (CI) 0.41-1.07; 5 trials] and nonvertebral fractures (RR 0.87, 95% CI 0.71-1.08; 6 trials). HRT had a consistent effect on bone mineral density (BMD) at all sites. The difference between HRT and control in the percent change in bone density at 2 yr was 6.76 (5.83, 7.89; 21 trials) at the lumbar spine and 4.53 (3.68, 5.36; 14 trials) and 4.12 (3.45, 4.80; 9 trials) at the forearm and femoral neck, respectively. CONCLUSIONS: HRT has a consistent, favorable and large effect on bone density at all sites. The data show a nonsignificant trend toward a reduced incidence in vertebral and nonvertebral fractures.

Estrogen Replacement Therapy↗

PubMed2002

Meta-analyses of therapies for postmenopausal osteoporosis. VI. Meta-analysis of calcitonin for the treatment of postmenopausal osteoporosis.

OBJECTIVE: To review the effect of calcitonin on bone density and fractures in postmenopausal women. DATA SOURCE: We searched MEDLINE and EMBASE from 1966 to 2000 and examined citations of relevant articles and the proceedings of international osteoporosis meetings. We contacted osteoporosis investigators to identify additional studies and primary authors for unpublished data. STUDY SELECTION: We included 30 studies that randomized women to calcitonin or an alternative (placebo or calcium and/or vitamin D) and measured bone density or fracture incidence for at least 1 yr. DATA EXTRACTION: For each trial, three independent reviewers assessed the methodological quality and abstracted data. DATA SYNTHESIS: Calcitonin reduced the incidence of vertebral fractures, with a pooled relative risk (RR) of 0.46 [95% confidence interval (CI) 0.25-0.87, P = 0.02, n = 1404, 4 trials]. However, the RR from the one relatively large randomized controlled trial (RCT) was 0.79 (95% CI 0.62-1.00, P = 0.05, n = 1108). For nonvertebral fractures, the pooled RR was 0.52 (95% CI 0.22-1.23, P = 0.14, n = 1481, 3 trials). Once again, the single large trial showed a less impressive effect than the smaller trials (RR 0.80, 95% CI 0.59-1.09, P = 0.16, n = 1245). For bone density of the lumbar spine, the pooled weekly dose of 250 to 2800 IU per week resulted in significant increase in the weighted mean difference (WMD) of 3.74 (2.04-5.43, P < 0.01, n = 2260, 24 trials). The combined forearm showed a similar effect, with a WMD of 3.02 (95% CI 0.98-5.07, P < 0.01, n = 468, 9 trials). At the femoral neck, the pooled weighted mean difference showed a nonsignificant trend toward benefit, WMD 3.80 (95% CI -0.32-7.91, P = 0.07, 9 trials, n = 513). Methodologically weaker studies tended to show greater effects on bone density, and the lumbar spine results suggested the possibility of publication bias. CONCLUSIONS: Calcitonin likely increases bone density in postmenopausal women predominantly at the lumbar spine and forearm for weekly doses of greater than 250 IU, although the true effect may be smaller than the pooled estimate would suggest. Calcitonin likely reduces the risk of vertebral fracture; its effect on nonvertebral fracture remains uncertain.

Calcitonin↗

PubMed2002

Meta-analyses of therapies for postmenopausal osteoporosis. VII. Meta-analysis of calcium supplementation for the prevention of postmenopausal osteoporosis.

OBJECTIVE: To summarize controlled trials examining the effect of calcium on bone density and fractures in postmenopausal women. DATA SOURCE: We searched MEDLINE and EMBASE up to 1998 and the Cochrane Controlled Register up to 2000, and we examined citations of relevant articles and proceedings of international meetings. We contacted osteoporosis investigators to identify additional studies, and primary authors for unpublished data. STUDY SELECTION: We included 15 trials (1806 patients) that randomized postmenopausal women to calcium supplementation or usual calcium intake in the diet and reported bone mineral density of the total body, vertebral spine, hip, or forearm, or recorded the number of fractures, and followed patients for at least 1 yr. DATA EXTRACTION: For each trial, three independent reviewers assessed the methodological quality and extracted data. DATA SYNTHESIS: We found calcium to be more effective than placebo in reducing rates of bone loss after two or more years of treatment. The pooled difference in percentage change from baseline was 2.05% [95% confidence interval (CI) 0.24-3.86] for total body bone density, 1.66% (95% CI 0.92-2.39) for the lumbar spine, 1.64% (95% CI 0.70-2.57) for the hip, and 1.91% (95% CI 0.33-3.50) for the distal radius. The relative risk (RR) of fractures of the vertebrae was 0.77, with a wide CI (95% CI 0.54-1.09); the RR for nonvertebral fractures was 0.86 (95% CI 0.43-1.72). CONCLUSIONS: Calcium supplementation alone has a small positive effect on bone density. The data show a trend toward reduction in vertebral fractures, but do not meaningfully address the possible effect of calcium on reducing the incidence of nonvertebral fractures.

Calcium↗

PubMed2002

Meta-analyses of therapies for postmenopausal osteoporosis. VIII: Meta-analysis of the efficacy of vitamin D treatment in preventing osteoporosis in postmenopausal women.

OBJECTIVE: To review the effect of vitamin D on bone density and fractures in postmenopausal women. DATA SOURCE: We searched MEDLINE and EMBASE from 1966 to 1999 and examined citations of relevant articles and proceedings of international meetings. We contacted osteoporosis investigators and primary authors to identify additional studies and to obtain unpublished data. STUDY SELECTION: We included 25 trials that randomized women to standard or hydroxylated vitamin D with or without calcium supplementation or a control and measured bone density or fracture incidence for at least 1 yr. DATA EXTRACTION: For each trial, three independent reviewers assessed the methodological quality and abstracted data. DATA SYNTHESIS: Vitamin D reduced the incidence of vertebral fractures [relative risk (RR) 0.63, 95% confidence interval (CI) 0.45-0.88, P < 0.01) and showed a trend toward reduced incidence of nonvertebral fractures (RR 0.77, 95% CI 0.57-1.04, P = 0.09). Most patients in the trials that evaluated vertebral fractures received hydroxylated vitamin D, and most patients in the trials that evaluated nonvertebral fractures received standard vitamin D. Hydroxylated vitamin D had a consistently larger impact on bone density than did standard vitamin D. For instance, total body differences in percentage change between hydroxylated vitamin D and control were 2.06 (0.72, 3.40) and 0.40 (-0.25, 1.06) for standard vitamin D. At the lumbar spine and forearm sites, hydroxylated vitamin D doses above 50 microg yield larger effects than lower doses. Vitamin D resulted in an increased risk of discontinuing medication in comparison to control as a result of either symptomatic adverse effects or abnormal laboratory results (RR 1.37, 95% CI 1.01-1.88), an effect that was similar in trials of standard and hydroxylated vitamin D. CONCLUSIONS: Vitamin D decreases vertebral fractures and may decrease nonvertebral fractures. The available data are uninformative regarding the relative effects of standard and hydroxylated vitamin D.

Female↗