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1.  Osteoporosis: The connection to urologic health 
Canadian Urological Association Journal  2014;8(7-8 Suppl 5):S156-S158.
Men with prostate cancer are often treated with androgen deprivation therapy (ADT), which is associated with reduced bone mineral density (BMD) and a higher risk for fractures. Maintenance of optimum bone health throughout the natural course of prostate cancer is an important aspect in the management of this patient population. Bone targeted therapies, such as bisphosphonates and the RANK ligand inhibitor denosumab, have been demonstrated to reduce skeletal-related events in patients with metastatic cancer, while denosumab has also been shown to reduce the risk of fracture in men undergoing ADT for prostate cancer.
PMCID: PMC4145699  PMID: 25243042
2.  Effectiveness and Cost-Effectiveness of Blood Pressure Screening in Adolescents in the United States 
The Journal of pediatrics  2010;158(2):257-64.e1-7.
To compare the long-term effectiveness and cost-effectiveness of 3 approaches to managing elevated blood pressure (BP) in adolescents in the United States: no intervention, “screen-and-treat,” and population-wide strategies to lower the entire BP distribution.
Study design
We used a simulation model to combine several data sources to project the lifetime costs and cardiovascular outcomes for a cohort of 15-year-old U.S. adolescents under different BP approaches and conducted cost-effectiveness analysis. We obtained BP distributions from the National Health and Nutrition Examination Survey 1999–2004 and used childhood-to-adult longitudinal correlation analyses to simulate the tracking of BP. We then used the coronary heart disease policy model to estimate lifetime coronary heart disease events, costs, and quality-adjusted life years (QALY).
Among screen-and-treat strategies, finding and treating the adolescents at highest risk (eg, left ventricular hypertrophy) was most cost-effective ($18 000/QALY [boys] and $47 000/QALY [girls]). However, all screen-and-treat strategies were dominated by population-wide strategies such as salt reduction (cost-saving [boys] and $650/ QALY [girls]) and increasing physical education ($11 000/QALY [boys] and $35 000/QALY [girls]).
Routine adolescents BP screening is moderately effective, but population-based BP interventions with broader reach could potentially be less costly and more effective for early cardiovascular disease prevention and should be implemented in parallel.
PMCID: PMC4007283  PMID: 20850759
3.  Bisphosphonates for treatment of osteoporosis 
Canadian Family Physician  2014;60(4):324-333.
To outline the efficacy and risks of bisphosphonate therapy for the management of osteoporosis and describe which patients might be eligible for bisphosphonate “drug holiday.”
Quality of evidence
MEDLINE (PubMed, through December 31, 2012) was used to identify relevant publications for inclusion. Most of the evidence cited is level II evidence (non-randomized, cohort, and other comparisons trials).
Main message
The antifracture efficacy of approved first-line bisphosphonates has been proven in randomized controlled clinical trials. However, with more extensive and prolonged clinical use of bisphosphonates, associations have been reported between their administration and the occurrence of rare, but serious, adverse events. Osteonecrosis of the jaw and atypical subtrochanteric and diaphyseal femur fractures might be related to the use of bisphosphonates in osteoporosis, but they are exceedingly rare and they often occur with other comorbidities or concomitant medication use. Drug holidays should only be considered in low-risk patients and in select patients at moderate risk of fracture after 3 to 5 years of therapy.
When bisphosphonates are prescribed to patients at high risk of fracture, their antifracture benefits considerably outweigh their potential for harm. For patients taking bisphosphonates for 3 to 5 years, reassess the need for ongoing therapy.
PMCID: PMC4046542  PMID: 24733321
4.  Les bisphosphonates dans le traitement de l’ostéoporose 
Canadian Family Physician  2014;60(4):e197-e207.
Exposer l’efficacité et les risques du traitement par les bisphosphonates dans la prise en charge de l’ostéoporose et décrire les patients qui seraient de bons candidats aux congés thérapeutiques.
Qualité des données
Une recherche dans MEDLINE (PubMed, jusqu’au 31 décembre 2012) a permis de relever les publications pertinentes pour l’inclusion. La plupart des données probantes citées sont de niveau II (tirées d’essais non randomisés, de cohorte et d’autres essais comparatifs).
Message principal
L’efficacité des bisphosphonates de premier recours homologués pour la prévention des fractures a été éprouvée dans le cadre d’essais cliniques randomisés et contrôlés. Cependant, l’usage clinique répandu et prolongé des bisphosphonates a donné lieu à des rapports de manifestations indésirables rares, mais graves. L’ostéonécrose maxillaire et les fractures atypiques sous-trochantériennes ou diaphysaires du fémur seraient liées à l’emploi des bisphosphonates dans le traitement de l’ostéoporose, mais ces manifestations sont extrêmement rares et lorsqu’elles surviennent, elles sont accompagnées d’autres comorbidités ou de l’emploi concomitant de médicaments. Les congés thérapeutiques ne peuvent être envisagés que chez les patients à faible risque et dans un groupe restreint de patients dont le risque de fracture est modéré après un traitement de 3 à 5 ans.
Lorsque les bisphosphonates sont prescrits à des patients dont le risque de fracture est élevé, leur effet de prévention des fractures l’emporte de loin sur leurs torts potentiels. Chez les patients qui prennent des bisphosphonates depuis 3 à 5 ans, il faut réévaluer le besoin de poursuivre le traitement.
PMCID: PMC4046553
5.  Randomized clinical trial of the timing it right stroke family support program: research protocol 
Family caregivers provide invaluable support to stroke survivors during their recovery, rehabilitation, and community re-integration. Unfortunately, it is not standard clinical practice to prepare and support caregivers in this role and, as a result, many experience stress and poor health that can compromise stroke survivor recovery and threaten the sustainability of keeping the stroke survivor at home. We developed the Timing it Right Stroke Family Support Program (TIRSFSP) to guide the timing of delivering specific types of education and support to meet caregivers’ evolving needs. The objective of this multi-site randomized controlled trial is to determine if delivering the TIRSFSP across the stroke care continuum improves caregivers’ sense of being supported and emotional well-being.
Our multi-site single-blinded randomized controlled trial will recruit 300 family caregivers of stroke survivors from urban and rural acute care hospitals. After completing a baseline assessment, participants will be randomly allocated to one of three groups: 1) TIRSFSP guided by a stroke support person (health care professional with stroke care experience), delivered in-person during acute care and by telephone for approximately the first six to 12 months post-stroke, 2) caregiver self-directed TIRSFSP with an initial introduction to the program by a stroke support person, or 3) standard care receiving the educational resource “Let’s Talk about Stroke” prepared by the Heart and Stroke Foundation. Participants will complete three follow-up quantitative assessments 3, 6, and 12-months post-stroke. These include assessments of depression, social support, psychological well-being, stroke knowledge, mastery (sense of control over life), caregiving assistance provided, caregiving impact on everyday life, and indicators of stroke severity and disability. Qualitative methods will also be used to obtain information about caregivers’ experiences with the education and support received and the impact on caregivers’ perception of being supported and emotional well-being.
This research will determine if the TIRSFSP benefits family caregivers by improving their perception of being supported and emotional well-being. If proven effective, it could be recommended as a model of stroke family education and support that meets the Canadian Stroke Best Practice Guideline recommendation for providing timely education and support to families through transitions.
Trial registration NCT00958607.
PMCID: PMC3898562  PMID: 24433234
Stroke; Caregiver; Mixed methods; Randomized controlled trial; Social support; Education; Longitudinal
8.  A Scoping Review of Strategies for the Prevention of Hip Fracture in Elderly Nursing Home Residents 
PLoS ONE  2010;5(3):e9515.
Elderly nursing home residents are at increased risk of hip fracture; however, the efficacy of fracture prevention strategies in this population is unclear.
We performed a scoping review of randomized controlled trials of interventions tested in the long-term care (LTC) setting, examining hip fracture outcomes.
We searched for citations in 6 respective electronic searches, supplemented by hand searches. Two reviewers independently reviewed all citations and full-text papers; consensus was achieved on final inclusion. Data was abstracted in duplicate.
We reviewed 22,349 abstracts or citations and 949 full-text papers. Data from 20 trials were included: 7 - vitamin D (n = 12,875 participants), 2 - sunlight exposure (n = 522), 1 - alendronate (n = 327), 1 - fluoride (n = 460), 4 – exercise or multimodal interventions (n = 8,165), and 5 - hip protectors (n = 2,594). Vitamin D, particularly vitamin D3 ≥800 IU orally daily, reduced hip fracture risk. Hip protectors reduced hip fractures in included studies, although a recent large study not meeting inclusion criteria was negative. Fluoride and sunlight exposure did not significantly reduce hip fractures. Falls were reduced in three studies of exercise or multimodal interventions, with one study suggesting reduced hip fractures in a secondary analysis. A staff education and risk assessment strategy did not significantly reduce falls or hip fractures. In a study underpowered for fracture outcomes, alendronate did not significantly reduce hip fractures in LTC.
The intervention with the strongest evidence for reduction of hip fractures in LTC is Vitamin D supplementation; more research on other interventions is needed.
PMCID: PMC2831075  PMID: 20209088
9.  Bone Disease in Thalassemia: A Frequent and Still Unresolved Problem 
Adults with β thalassemia major frequently have low BMD, fractures, and bone pain. The purpose of this study was to determine the prevalence of low BMD, fractures, and bone pain in all thalassemia syndromes in childhood, adolescence, and adulthood, associations of BMD with fractures and bone pain, and etiology of bone disease in thalassemia. Patients of all thalassemia syndromes in the Thalassemia Clinical Research Network, ≥6 yr of age, with no preexisting medical condition affecting bone mass or requiring steroids, participated. We measured spine and femur BMD and whole body BMC by DXA and assessed vertebral abnormalities by morphometric X-ray absorptiometry (MXA). Medical history by interview and review of medical records, physical examinations, and blood and urine collections were performed. Three hundred sixty-one subjects, 49% male, with a mean age of 23.2 yr (range, 6.1–75 yr), were studied. Spine and femur BMD Z-scores < −2 occurred in 46% and 25% of participants, respectively. Greater age, lower weight, hypogonadism, and increased bone turnover were strong independent predictors of low bone mass regardless of thalassemia syndrome. Peak bone mass was suboptimal. Thirty-six percent of patients had a history of fractures, and 34% reported bone pain. BMD was negatively associated with fractures but not with bone pain. Nine percent of participants had uniformly decreased height of several vertebrae by MXA, which was associated with the use of iron chelator deferoxamine before 6 yr of age. In patients with thalassemia, low BMD and fractures occur frequently and independently of the particular syndrome. Peak bone mass is suboptimal. Low BMD is associated with hypogonadism, increased bone turnover, and an increased risk for fractures.
PMCID: PMC3276604  PMID: 18505376
DXA; BMD; fractures; vertebral morphometry; thalassemia
11.  Vitamin K Supplementation in Postmenopausal Women with Osteopenia (ECKO Trial): A Randomized Controlled Trial 
PLoS Medicine  2008;5(10):1-12.
Vitamin K has been widely promoted as a supplement for decreasing bone loss in postmenopausal women, but the long-term benefits and potential harms are unknown. This study was conducted to determine whether daily high-dose vitamin K1 supplementation safely reduces bone loss, bone turnover, and fractures.
Methods and Findings
This single-center study was designed as a 2-y randomized, placebo-controlled, double-blind trial, extended for earlier participants for up to an additional 2 y because of interest in long-term safety and fractures. A total of 440 postmenopausal women with osteopenia were randomized to either 5 mg of vitamin K1 or placebo daily. Primary outcomes were changes in BMD at the lumbar spine and total hip at 2 y. Secondary outcomes included changes in BMD at other sites and other time points, bone turnover markers, height, fractures, adverse effects, and health-related quality of life. This study has a power of 90% to detect 3% differences in BMD between the two groups. The women in this study were vitamin D replete, with a mean serum 25-hydroxyvitamin D level of 77 nmol/l at baseline. Over 2 y, BMD decreased by −1.28% and −1.22% (p = 0.84) (difference of −0.06%; 95% confidence interval [CI] −0.67% to 0.54%) at the lumbar spine and −0.69% and −0.88% (p = 0.51) (difference of 0.19%; 95% CI −0.37% to 0.75%) at the total hip in the vitamin K and placebo groups, respectively. There were no significant differences in changes in BMD at any site between the two groups over the 2- to 4-y period. Daily vitamin K1 supplementation increased serum vitamin K1 levels by 10-fold, and decreased the percentage of undercarboxylated osteocalcin and total osteocalcin levels (bone formation marker). However, C-telopeptide levels (bone resorption marker) were not significantly different between the two groups. Fewer women in the vitamin K group had clinical fractures (nine versus 20, p = 0.04) and fewer had cancers (three versus 12, p = 0.02). Vitamin K supplements were well-tolerated over the 4-y period. There were no significant differences in adverse effects or health-related quality of life between the two groups. The study was not powered to examine fractures or cancers, and their numbers were small.
Daily 5 mg of vitamin K1 supplementation for 2 to 4 y does not protect against age-related decline in BMD, but may protect against fractures and cancers in postmenopausal women with osteopenia. More studies are needed to further examine the effect of vitamin K on fractures and cancers.
Trial registration: (#NCT00150969) and Current Controlled Trials (#ISRCTN61708241)
Angela Cheung and colleagues investigate whether vitamin K1 can prevent bone loss among postmenopausal women with osteopenia.
Editors' Summary
Osteoporosis is a bone disease in which the bones gradually become less dense and more likely to break. In the US, 10 million people have osteoporosis and 18 million have osteopenia, a milder condition that precedes osteoporosis. In both conditions, insufficient new bone is made and/or too much old bone is absorbed. Although bone appears solid and unchanging, very little bone in the human body is more than 10 y old. Old bone is continually absorbed and new bone built using calcium, phosphorous, and proteins. Because the sex hormones control calcium and phosphorous deposition in the bones and thus bone strength, the leading cause of osteoporosis in women is reduced estrogen levels after menopause. In men, an age-related decline in testosterone levels can cause osteoporosis. Most people discover they have osteoporosis only when they break a bone, but the condition can be diagnosed and monitored using bone mineral density (BMD) scans. Treatments can slow down or reverse bone loss (antiresorptive therapies) and some (bone formation therapies) can even make bone and build bone tissue.
Why Was This Study Done?
Although regular exercise and a healthy diet can help to keep bones strong, other ways of preventing osteoporosis are badly needed. Recently, the lay media has promoted vitamin K supplements as a way to reduce bone loss in postmenopausal women. Vitamin K (which is found mainly in leafy green vegetables) is required for a chemical modification of proteins called carboxylation. This modification is essential for the activity of three bone-building proteins. In addition, there is some evidence that low bone density and fractures are associated with a low vitamin K intake. However, little is known about the long-term benefits or harms of vitamin K supplements. In this study, the researchers investigate whether a high-dose daily vitamin K supplement can safely reduce bone loss, bone turnover, and fractures in postmenopausal women with osteopenia in a randomized controlled trial called the “Evaluation of the Clinical Use of Vitamin K Supplementation in Post-Menopausal Women With Osteopenia” (ECKO) trial.
What Did the Researchers Do and Find?
In the study, 440 postmenopausal women with osteopenia were randomized to receive 5mg of vitamin K1 (the type of vitamin K in North American food; the recommended daily adult intake of vitamin K1 is about 0.1 mg) or an inactive tablet (placebo) daily for 2 y; 261 of the women continued their treatment for 2 y to gather information about the long-term effects of vitamin K1 supplementation. All the women had regular bone density scans of their lower back and hips and were examined for fractures and for changes in bone turnover. After 2 y and after 4 y, lower back and hip bone density measurements had decreased by similar amounts in both treatment groups. The women who took vitamin K1 had 10-fold higher amounts of vitamin K1 in their blood than the women who took placebo and lower amounts of a bone formation marker; the levels of a bone resorption marker were similar in both groups. Over the 4-y period, fewer women in the vitamin K group had fractures (nine versus 20 women in the placebo group), and fewer had cancer (three versus 12). Finally, vitamin K supplementation was well tolerated over the 4-y period and adverse health effects were similar in the two treatment groups.
What Do These Findings Mean?
These findings indicate that a high daily dose of vitamin K1 provides no protection against the age-related decline in bone density in postmenopausal women with osteopenia, but that vitamin K1 supplementation may protect against fractures and cancers in these women. The apparent contradiction between the effects of vitamin K1 on bone density and on fractures could mean that vitamin K1 supplements strengthen bone by changing factors other than bone density, e.g., by changing its fine structure rather than making it denser. However, because so few study participants had fractures, the difference in the fracture rate between the two treatment groups might have occurred by chance. Larger studies are therefore needed to examine the effect of vitamin K1 on fractures (and on cancer) and, until these are done, high-dose vitamin K1 supplementation should not be recommended for the prevention of osteoporosis.
Additional Information.
Please access these Web sites via the online version of this summary at
The US National Institute of Arthritis and Musculoskeletal and Skin Diseases provides detailed information about osteoporosis (in English and Spanish) and links to other resources, including an interactive web tool called Check Up On Your Bones
MedlinePlus provides links to additional information about osteoporosis (in English and Spanish)
The MedlinePlus Encyclopedia has a page about vitamin K
The UK Food Standards Agency provides information about vitamin K
Full details about the ECKO trial are available on the Web site
The Canadian Task Force for Preventive Health Care provides recommendations on the prevention of osteoporosis and osteoporotic fractures in postmenopausal women
Osteoporosis Canada provides information on current topics related to osteoporosis
PMCID: PMC2566998  PMID: 18922041
12.  Population mortality during the outbreak of Severe Acute Respiratory Syndrome in Toronto 
BMC Public Health  2007;7:93.
Extraordinary infection control measures limited access to medical care in the Greater Toronto Area during the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak. The objective of this study was to determine if the period of these infection control measures was associated with changes in overall population mortality due to causes other than SARS.
Observational study of death registry data, using Poisson regression and interrupted time-series analysis to examine all-cause mortality rates (excluding deaths due to SARS) before, during, and after the SARS outbreak. The population of Ontario was grouped into the Greater Toronto Area (N = 2.9 million) and the rest of Ontario (N = 9.3 million) based upon the level of restrictions on delivery of clinical services during the SARS outbreak.
There was no significant change in mortality in the Greater Toronto Area before, during, and after the period of the SARS outbreak in 2003 compared to the corresponding time periods in 2002 and 2001. The rate ratio for all-cause mortality during the SARS outbreak was 0.99 [95% Confidence Interval (CI) 0.93–1.06] compared to 2002 and 0.96 [95% CI 0.90–1.03] compared to 2001. An interrupted time series analysis found no significant change in mortality rates in the Greater Toronto Area associated with the period of the SARS outbreak.
Limitations on access to medical services during the 2003 SARS outbreak in Toronto had no observable impact on short-term population mortality. Effects on morbidity and long-term mortality were not assessed. Efforts to contain future infectious disease outbreaks due to influenza or other agents must consider effects on access to essential health care services.
PMCID: PMC1894965  PMID: 17535440
13.  Perimenopausal and Postmenopausal Health 
BMC Women's Health  2004;4(Suppl 1):S23.
Health Issue
The average age of natural menopause in Western societies is estimated to be 51 years; women in Canada can therefore expect to live, on average, a third of their lives in post-menopausal years. During these years women are at increased risk of chronic diseases such as osteoporosis and cardiovascular disease.
Key Findings
Clinical and epidemiological data on women in perimenopause are limited. There are no adequate Canadian data on symptom severity and prevalence among perimenopausal and postmenopausal women. Scientific evidence is lacking to support or refute claims that commonly used botanical products can offer therapeutic relief of menopausal symptoms.
Recent data from the Women's Health Initiative suggest that combined estrogen plus therapy increases the risk of stroke, coronary artery disease and breast cancer. Hormone therapy is no longer recommended for the prevention of chronic diseases for asymptomatic women. Stroke is an important issue for perimenopausal and postmenopausal women and sex differences may exist in the progestin treatment of stroke. Osteoporosis affects an estimated one in six women over the age of 50.
Data Gaps and Recommendations
There is a need to conduct clinical and epidemiological research aimed at better understanding the menopausal transition and defining its clinical phases. Investigations aimed at alternative combinations and doses of hormone therapy and non-pharmaceutical alternatives in light of known risks and benefits are also necessary. Health care practitioners and women need to be educated on the risks and effective treatment related to cardiovascular disease so they can present for treatment more quickly and receive the most effective therapies.
PMCID: PMC2096694  PMID: 15345086
16.  Risk of death among homeless women: a cohort study and review of the literature 
Homeless people are at high risk for illness and have higher death rates than the general population. Patterns of mortality among homeless men have been investigated, but less attention has been given to mortality rates among homeless women. We report mortality rates and causes of death in a cohort of women who used homeless shelters in Toronto. We also compare our results with those of other published studies of homeless women and with data for women in the general population.
A cohort of 1981 women not accompanied by dependent children who used homeless shelters in Toronto in 1995 was observed for death over a mean of 2.6 years. In addition, we analyzed data from published studies of mortality rates among homeless women in 6 other cities (Montreal, Copenhagen, Boston, New York, Philadelphia and Brighton, UK).
In Toronto, mortality rates were 515 per 100 000 person-years among homeless women 18–44 years of age and 438 per 100 000 person-years among those 45–64 years of age. Homeless women 18–44 years of age were 10 times more likely to die than women in the general population of Toronto. In studies from a total of 7 cities, the risk of death among homeless women was greater than that among women in the general population by a factor of 4.6 to 31.2 in the younger age group and 1.0 to 2.0 in the older age group. In 6 of the 7 cities, the mortality rates among younger homeless women and younger homeless men were not significantly different. In contrast, in 4 of the 6 cities, the mortality rates were significantly lower among older homeless women than among older homeless men.
Excess mortality is far greater among homeless women under age 45 years than among older homeless women. Mortality rates among younger homeless women often approach or equal those of younger homeless men. Efforts to reduce deaths of homeless women should focus on those under age 45.
PMCID: PMC385354  PMID: 15078846

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