Ann Cranney

Low bone mineral density and fracture burden in postmenopausal women

Background: The study objectives were to determine fracture rates in relation to bone mineral density at various central skeletal sites, using the World Health Organization definition for osteoporosis (T-score –2.5 or less), and to contrast fracture patterns among women 50 to 64 years of age with those among women 65 years of age and older. Methods: Historical cohort study with a mean observation period of 3.2 (standard deviation [SD] 1.5) years. The study group (16 505 women 50 years of age or older) was drawn from the Manitoba Bone Density Program database, which includes all bone mineral density results for Manitoba. Baseline density measurements for the lumbar spine and hip were performed with dual-energy x-ray absorptiometry. Outcomes included the percentage of osteoporotic fractures and the rates of fracture and excess fracture (per 1000 person-years) among postmenopausal women with osteopenia and osteoporosis relative to those with normal bone mineral density (according to the classification of the World Health Organization). Results: The mean age was 65 (SD 9) years, and the mean T-scores for all sites fell within the osteopenic category. There were 765 incident fractures (fracture rate 14.5 [95% confidence interval, CI, 13.5–15.6 [per 1000 person-years). Fracture rates were significantly higher among women 65 years of age or older than among women 50–64 years of age (21.6 [95% CI 19.7–23.4] v. 8.6 [95% CI 7.5–9.7] per 1000 person-years, p < 0.001). Although fracture rates were significantly higher among women with osteoporotic T-scores, most fractures occurred in women with nonosteoporotic values (min–max: 59.7%–67.8%). Interpretation: In this study, most of the postmenopausal women with osteoporotic fractures had nonosteoporotic bone mineral density values. This finding highlights the importance of considering key clinical risk factors that operate independently of bone mineral density (such as age) when assessing fracture risk.

Vitamin D in adult health and disease: a review and guideline statement from Osteoporosis Canada - summary

CMAJ • SEPTEMBER 7, 2010 • 182(12)

Celiac Disease: Evaluation of the Diagnosis and Dietary Compliance in Canadian Children

Objectives. We sought to characterize the clinical features at presentation as well as the associated disorders, family history, and evaluation of compliance with a gluten-free diet in children with celiac disease from across Canada. Study Design. All members (n = 5240) of the Canadian Celiac Association were surveyed with a questionnaire. Of the 2849 respondents with biopsy-confirmed celiac disease, 168 who were <16 years old provided the data reported here. Results. The mean age when surveyed was 9.1 ± 4.1 years, and 58% were female. Median age at diagnosis was 3.0 years with a range of 1 to 15 years. Presenting symptoms included abdominal pain (90%), weight loss (71%), diarrhea (65%), weakness (64%), nausea/vomiting (53%), anemia (40%), mood swings (37%), and constipation (30%). Almost one third of families consulted ≥2 pediatricians before confirmation of the diagnosis. Before the recognition of celiac disease, other diagnoses received by these children included anemia (15%), irritable bowel syndrome (11%), gastroesophageal reflux (8%), stress (8%), and peptic ulcer disease (4%). A serological test was performed to screen for celiac disease in 70% of those in this population. Eight percent had either type 1 diabetes mellitus or a first-degree relative with celiac disease. Almost all respondents (95%) reported strict adherence to a gluten-free diet, and 89% noted improved health. Reactions after accidental gluten ingestion developed in 54% of the children between 0.5 and 60 hours after ingestion with a median of 2.0 hours. Reactions included abdominal discomfort (87%), diarrhea (64%), bloating (57%), fatigue (37%), headache (24%), and constipation (8%), and most displayed >1 symptom. Although most adjusted well to their disease and diet, 10% to 20% reported major disruptions in lifestyle. Twenty-three percent felt angry all or most of the time about following a gluten-free diet. Only 15% avoided traveling all or most of the time, and during travel, 83% brought gluten-free food with them all of the time. More than half of the families avoided restaurants all or most of the time. Twenty-eight percent of the respondents found it extremely difficult to locate stores with gluten-free foods, and 27% reported extreme difficulty in finding gluten-free foods or determining if foods were free of gluten. Sixty-three percent of the respondents felt that the information supplied by the Canadian Celiac Association was excellent. Gastroenterologists provided excellent information to 44%, dietitians to 36%, and the family physician to 11.5%. When asked to select 2 items that would improve their quality of life, better labeling of gluten-containing ingredients was selected by 63%, more gluten-free foods in the supermarket by 49%, gluten-free choices on restaurant menus by 49%, earlier diagnosis of celiac disease by 34%, and better dietary counseling by 7%. Conclusions. In Canada, children with celiac disease present at all ages with a variety of symptoms and associated conditions. Delays in diagnosis are common. Most children are compliant with a gluten-free diet. A minority of these children experience difficulties in modifying their lifestyles, and gluten-free foods remain difficult to obtain.

The Canadian Celiac Health Survey

The purpose of this study was to characterize the diagnostic process, frequency of associated disorders, family history, and impact of a gluten-free diet in individuals with celiac disease. All members of the Canadian Celiac Association (n=5240) were surveyed with a questionnaire. Respondents included 2681 adults with biopsy-proven celiac disease. The mean age was 56 years. Most common presenting symptoms included abdominal pain (83%), diarrhea (76%), and weight loss (69%). The mean delay in diagnosis was 11.7 years. Diagnoses made prior to celiac disease included anemia (40%), stress (31%), and irritable bowel syndrome (29%). Osteoporosis was common. Prior to diagnosis, 27% of respondents consulted three or more doctors about their symptoms. Delays in diagnosis of celiac disease remain a problem. Associated medical conditions occur frequently. More accurate food labeling is needed. Improved awareness of celiac disease and greater use of serological screening tests may result in earlier diagnosis and reduced risk of associated conditions.

A meta-analysis of etidronate for the treatment of postmenopausal osteoporosis.

Abstract: The aim of the study was to review the effect of etidronate on bone density and fractures in postmenopausal women. We searched MEDLINE from 1966 to 1998, examined citations of relevant articles, and the proceedings of international osteoporosis meetings. We contacted osteoporosis investigators to identify additional studies, primary authors, and pharmaceutical industry sources for unpublished data. We included 13 trials that randomized women to etidronate or an alternative (placebo or calcium and/or vitamin D) and measured bone density for at least 1 year. For each trial, three independent reviewers assessed the methodologic quality and abstracted data. The data suggested a reduction in vertebral fractures with a pooled relative risk of 0.63 (95% CI 0.44 to 0.92). There was no effect on nonvertebral fractures (relative risk 0.99, (95% CI 0.69 to 1.42). Etidronate, relative to control, increased bone density after 1–3 years of treatment in the lumbar spine by 4.06% (95% CI 3.12 to 5.00), in the femoral neck by 2.35% (95% CI 1.66 to 3.04) and in the total body by 0.97% (95% CI 0.39 to 1.55). Effects were larger at 4 years, though the number of patients followed much smaller. Etidronate increases bone density in the lumbar spine and femoral neck for up to 4 years. The pooled estimates of fracture reduction with etidronate suggest a reduction in vertebral fractures, but no effect on nonvertebral fractures.

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.

Efficacy of food fortification on serum 25-hydroxyvitamin D concentrations: systematic review

BACKGROUND Many residents of the United States and Canada depend on dietary sources of vitamin D to help maintain vitamin D status. Because few natural food sources contain vitamin D, fortified foods may be required. OBJECTIVE We aimed to determine the effects of vitamin D-fortified foods on serum 25-hydroxyvitamin D [25(OH)D] concentrations. DESIGN We searched MEDLINE (1966 to June Week 3 2006), Embase, CINAHL, AMED, Biological Abstracts, and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) comparing vitamin D-fortified foods with a control and reporting serum 25(OH)D concentrations. Two reviewers independently determined study eligibility, assessed trial quality, and extracted relevant data. Disagreements were resolved by consensus. Meta-analyses of absolute mean change in 25(OH)D were conducted by using a random-effects model, with evaluation of heterogeneity. RESULTS Nine RCTs (n = 889 subjects) were included, of which 8 consistently showed a significant beneficial effect of food fortification on 25(OH)D concentrations. Although 7 RCTs (n = 585 subjects) potentially were meta-analyzable, we were unable to combine the overall results because of significant heterogeneity. The individual treatment effects ranged from 14.5 (95% CIs: 10.6, 18.4) nmol/L to 34.5 (17.64, 51.36) nmol/L (3.4-25 microg vitamin D/d). Subgroup analyses showed a reduction in heterogeneity and significant treatment effect when 4 trials that used milk as the fortified food source were combined. CONCLUSION Most trials were small in size and inadequately reported allocation concealment, but results showed that vitamin D-fortified foods improved vitamin D status in adults.

Development and pilot testing of a decision aid for postmenopausal women with osteoporosis

This studys aim was to develop and pilot test an evidence-based decision aid for postmenopausal women with osteoporosis who are considering options to prevent fractures. The aid was based on the Ottawa Decision Support Framework, and integrated evidence from our Cochrane systematic reviews. Following development by a panel of experts in osteoporosis and decision making, a user review panel of practitioners and women who had already made their decision about osteoporosis therapy reviewed the decision aid for acceptability. Then the decision aid was pilot tested using a before-after design in women at the point of decision making. Compared to baseline, there were statistically significant improvements in knowledge, realistic expectations and decreased decisional conflict. Our decision aid shows promise in preparing women for counseling about osteoporosis therapies. Long-term adherence to chosen therapy and quality of life will be evaluated in a randomized controlled trial.

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.

Systematic review of the benefits and harms of calcitriol and alfacalcidol for fractures and falls

Our objective was to conduct a systematic review on the benefits and harms of calcitriol and alfacalcidol in the reduction of fracture and fall risk. Randomized controlled trials (RCTs) comparing these agents to placebo or calcium and reporting fracture and fall incidence were retrieved from MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. Two reviewers independently determined study eligibility, assessed trial quality, and extracted data. Twenty-three RCTs were included (2139 participants), and 16 trials had sufficient data for meta-analysis. Vertebral fractures were not significantly reduced based on the combined results of 13 trials; however, subgroup analyses demonstrated a significant reduction with alfacalcidol [odds ratio (OR) = 0.50, 95% confidence interval (CI), 0.25–0.98], but not with calcitriol. There was a significant reduction in nonvertebral fractures (six trials, OR = 0.51, 95% CI, 0.30–0.88), and falls (two trials, OR = 0.66, 95% CI, 0.44–0.98). There was an increased risk of hypercalcemia (OR = 3.63, 95% CI, 1.51–8.73) and a trend toward an increased risk of hypercalciuria. There is evidence to suggest that these agents may reduce the incidence of nonvertebral fractures and falls; however, their benefit on vertebral fracture reduction may depend on the type of active vitamin D. Hypercalcemia and hypercalciuria are potential side effects.