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David A Hanley

Publications and source records attributed to David A Hanley.

35 records · Page 2Linked to original sources
PubMed2005

A systematic review of the effect of alendronate on bone mineral density in men.

Alendronate is known to increase bone mineral density (BMD) at the lumbar spine and hip in women, but less information is available in men. We conducted a systematic review of randomized controlled trials to determine whether oral alendronate improves BMD at the lumbar spine and hip in men with low bone mass or prevalent fractures, compared with men treated with placebo, calcium, or vitamin D. In three trials in men, BMD (measured by dual-energy X-ray absorptiometry) increased at 2-3 yr (compared to baseline) at the lumbar spine and femoral neck in alendronate-treated patients compared to controls. The pooled estimates of changes in BMD with 10 mg of alendronate daily compared to controls were as follows: 7.8% over 2-3 yr (95% confidence interval [CI] = 4.8- 10.8) at the lumbar spine and 3.8% (95% CI = 2.3-5.3) at the femoral neck (p < 0.001 for treatment effect in each analysis). Statistically significant heterogeneity of treatment effect was noted between trials. We conclude that 10 mg of oral daily alendronate is significantly associated with increase in BMD at the lumbar spine and hip in men over 2-3 yr and that these changes are similar to those previously observed in postmenopausal women.

Alendronate↗
PubMed2004

Risk factors associated with incident clinical vertebral and nonvertebral fractures in postmenopausal women: the Canadian Multicentre Osteoporosis Study (CaMos).

Utilizing data from the Canadian Multicentre Osteoporosis Study (CaMos), we examined the association between potential risk factors and incident vertebral and nonvertebral fractures. A total of 5,143 postmenopausal women were enrolled. Information collected during the study included data from the CaMos baseline and annually mailed fracture questionnaires, the Short Form 36 (SF-36), the Health Utilities Index, and physical measurements. Participants were followed for 3 years. Postmenopausal women were classified into four groups according to their incident fracture status since baseline: those without a new fracture; those with a new clinically recognized vertebral fracture; those with an incident nonvertebral fracture at the wrist, hip, humerus, pelvis, or ribs (main nonvertebral fracture group); and those with any new nonvertebral fracture (any-nonvertebral-fracture group). We performed multivariate Cox proportional hazard analysis using all possible risk factors to determine the association between risk factors and the time to the first minimal trauma fracture. Best predictive models were also determined using variables that were included in the full models. The Bayesian information criterion was used for model selection. For all analyses, relative risks and associated 95% confidence intervals were calculated. During the follow-up period, 34, 163, and 280 women developed a vertebral, a main nonvertebral, or any nonvertebral fracture, respectively. The best predictive models indicated that a five point lower quality of life as measured by the SF-36 physical component summary score was associated with relative risks of 1.21 (95% CI, 1.02 to 1.44), 1.17 (95% CI, 1.07 to 1.28), and 1.19 (95% CI, 1.11 to 1.27) for incident vertebral, main nonvertebral, and all nonvertebral fractures, respectively. In addition, for a one standard deviation (SD=0.12) lower femoral neck BMD, the relative risks for incident vertebral, main nonvertebral, and any nonvertebral fractures increased by 2.73 (95% CI, 1.74 to 4.28), 1.39 (95% CI, 1.06 to 1.82), and 1.34 (95% CI, 1.09 to 1.65), respectively. Furthermore, various anthropometric measures, disease conditions, and medications are associated with a new fracture. Identifying postmenopausal women at risk is important given that fracture prevention therapies are now available.

Adult↗
PubMed2004

A controlled trial to increase detection and treatment of osteoporosis in older patients with a wrist fracture.

BACKGROUND: Despite the high risk for future fractures and the availability of effective treatments, fewer than 10% to 20% of patients who sustain a fragility fracture are tested or treated for osteoporosis. OBJECTIVES: To improve rates of testing and treatment for osteoporosis in patients with wrist fractures who are seen in the emergency department. DESIGN: Nonrandomized, controlled trial with blinded ascertainment of outcomes. SETTING: Emergency departments in Edmonton, Alberta, Canada. PATIENTS: Persons 50 years of age or older who were treated for a wrist fracture and their physicians. Patients admitted to the hospital or treated for osteoporosis were excluded. Overall, 572 consecutive patients with fractures were screened, and 102 patients (55 intervention, 47 control) and 101 physicians were studied. MEASUREMENTS: The primary end point was the prescription of osteoporosis treatment 6 months after fracture. Secondary end points included rates of testing for bone mineral density and patients' knowledge, satisfaction, and quality of life. INTERVENTION: Faxed physician reminders that contained osteoporosis treatment guidelines endorsed by local opinion leaders and patient education. Control patients received usual care and information about falls and home safety. RESULTS: The median patient age was 66 years. Most patients were female (78%) and white (79%); 70% of patients reported a previous fracture, and 22% had a fall with injury in the previous year. The intervention increased the rates of testing for bone mineral density to 62% (vs. 17% for controls; adjusted relative increase, 3.6 [P < 0.001]) and the rates of osteoporosis treatment to 40% (vs. 10% for controls; adjusted relative increase, 3.8 [P = 0.002]) within 6 months of fracture. Intervention patients were more likely to report a diagnosis of osteoporosis, but other patient-reported outcomes did not differ significantly between groups. LIMITATIONS: This was a small, nonrandomized, controlled study with process-based outcomes. CONCLUSIONS: In a multifaceted intervention directed at patients and their physicians, the rates of testing and treatment for osteoporosis after emergency department care for a fragility fracture were more than 3 times those of controls.

Aged↗
PubMed2004

Osteoporosis in men: epidemiology, diagnosis, prevention, and treatment.

BACKGROUND: Osteoporosis and fragility fractures in men account for substantial health care expenditures and decreased quality of life. OBJECTIVE: This article reviews the most current information about the epidemiology, diagnosis, prevention, and treatment of osteoporosis in men. METHODS: Relevant literature was identified through a search of MEDLINE (1966-June 2003) limited to English-language studies in men. The search terms included fractures, bone density, or osteoporosis plus either epidemiology, diagnosis, prevention, control, or therapy. Additional search terms included specific subtopics (eg, bisphosphonates, calcium, exercise, parathyroid hormone). The authors contributed additional relevant publications. RESULTS: Morbidity after fragility fracture is at least as high in men as in women, and the rate of fracture-related mortality 1 year hip fracture is approximately double in men compared with women. The bioavailable fraction of testosterone slowly declines into the ninth decade in men. There is evidence that the effect of estrogen on bone is greater than that of testosterone in men. Diagnosing osteoporosis in men is complicated by a lack of consensus on how it should be defined. Significant risk factors for osteoporosis or fracture include low bone mineral density, previous fragility fracture, maternal history of fracture, marked hypogonadism, smoking, heavy alcohol intake or alcoholism, low calcium intake, low body mass or body mass index, low physical activity, use of bone-resorbing medication such as glucocorticoids, and the presence of such conditions as hyperthyroidism, hyperparathyroidism, and hypercalciuria. Prevention is paramount and should begin in childhood. During adulthood, calcium (1000-1500 mg/d), vitamin D (400-800 IU/d), and adequate physical activity play crucial preventive roles. When treatment is indicated, the bisphosphonates are the first choice, whereas there is less support for the use of calcitonin or androgen therapy. Parathyroid hormone (1-34) is a promising anabolic therapy. There is also strong evidence for the use of bisphosphonates for the treatment of glucocorticoid-induced osteoporosis.

Androgens↗
PubMed2004

The canadian health claim for calcium, vitamin d and osteoporosis.

To provide evidence for or against allowing a health claim for calcium in Canada, we undertook a review of the current U.S. health claim for calcium and osteoporosis, and also reviewed the scientific literature published since that health claim was first proposed and reviewed by the U.S. Food and Drug Administration in 1991 and adopted in 1993. Our objectives were 1) to determine if the science behind the claim was still valid, and if so, 2) to recommend any new wording to the claim, if warranted, prior to implementation in Canada. Based on a review of the evidence (to May 2000) related to the various claim elements, the following health claim for calcium has been established in Canada: A healthy diet with adequate calcium and vitamin D, and regular physical activity, help to achieve strong bones and may reduce the risk of osteoporosis. The compositional criteria for foods bearing this claim are that the food must provide at least 200 mg calcium per serving and that the phosphorus content (excluding that provided by phytate) must be less than the calcium content.

Calcium, Dietary↗
PubMed2004

IGF-I and testosterone levels as predictors of bone mineral density in healthy, community-dwelling men.

OBJECTIVE: Age-related decline in IGF-I and gonadal hormones have been postulated to play an important role in the pathogenesis of age-related bone loss in men. In this cross-sectional study, the relation between serum IGF-I and gonadal hormones with bone mineral density (BMD) was examined in community-dwelling men. DESIGN AND SUBJECTS: Serum IGF-I, testosterone and BMD were examined in 61 community-dwelling men over the age of 27, who were randomly selected from the Calgary cohort of 1000 subjects in the Canadian Multicentre Osteoporosis Study. In the present study, IGF-I, serum testosterone, SHBG, free androgen index (FAI), parathyroid hormone (PTH), 25-hydroxy-vitamin D [25(OH)D] and other markers of bone turnover were measured. BMD was measured at the spine and hip (HOLOGIC 4500). Simple linear regression was used to assess the linear relation between IGF-I, testosterone, BMD and other biochemical markers of bone metabolism and potential confounding variables and subsequent multivariate regression models were constructed separately for each BMD measurement to assess the importance of IGF-I and testosterone in the presence of potential confounding variables. RESULTS: Serum IGF-I, FAI and SHBG significantly decreased as a function of age, whereas serum levels of PTH increased. Only 25(OH)D, total testosterone and FAI were positively associated with serum IGF-I after adjusting for age and BMI. Multiple linear regression models revealed that IGF-I was a significant predictor of BMD at the total hip, femoral neck and femoral trochanter neck (P < or = 0.001). In contrast, the FAI was a significant predictor of BMD at the lumbar spine and wards area (P < or = 0.011), and SHBG was a significant predictor at the total hip and femoral trochanter (P < or = 0.045). CONCLUSION: These data support the hypothesis that the age-related decline in bone mass in men is associated with declining levels of IGF-I and testosterone.

25-Hydroxyvitamin D 2↗
PubMed2004

Standards and guidelines for performing central dual-energy x-ray absorptiometry in premenopausal women, men, and children.

The Canadian Panel of the International Society for Clinical Densitometry has developed standards in order to establish the minimum level of acceptable performance for the practice of bone densitometry in Canada. Previously, this group addressed the performance of densitometry in postmenopausal women. This report addresses the use of densitometry in men, premenopausal women, and children with a focus on dual-energy X-ray absorptiometry.

Absorptiometry, Photon↗
PubMed2004

Are there differences between men and women prescribed bisphosphonate therapy in canadian subspecialty osteoporosis practices?

OBJECTIVE: To determine if there are differences between men and women referred for treatment of osteoporosis in Canada. METHODS: We performed an observational study of 1588 patients (163 men, 1425 women), 50 years of age and older, who were prescribed cyclic etidronate or alendronate for treatment of osteoporosis or osteopenia and had at least 2 years of followup registered in the Canadian Database for Osteoporosis and Osteopenia Patients (CANDOO). Comparisons of characteristics between men and women were performed using Pearson chi-square test, Student's t test, or a Kruskal-Wallis test, whichever was most appropriate. RESULTS: Mean baseline femoral neck and lumbar spine bone mineral densities were significantly higher in men than women at both the femoral neck and lumbar spine (p < 0.05, respectively). Men had double the rate of prevalent vertebral fractures (44%, 72/163) compared to women (22%, 315/1425; p < 0.001) and triple the rate of multiple prevalent vertebral fractures (10%, 17/163) compared to women (3%, 37/1425, p < 0.001). Furthermore, men were twice as likely as women to sustain a fracture within 2 years of starting treatment during observation in the CANDOO study (men: 4%, 7/163, women: 2%, 24/1425, p = 0.033). CONCLUSION: Osteoporosis may be under-recognized in men until the condition is at an advanced stage. A form of gender bias may exist in recognition and treatment (or referral for treatment) of osteoporosis in men.

Aged↗
PubMed2003

Adherence to bisphosphonates and hormone replacement therapy in a tertiary care setting of patients in the CANDOO database.

Therapies for osteoporosis must be taken for at least 1 year to be effective. The purpose of this study was to determine the difference in adherence to etidronate, alendronate and hormone replacement therapy in a group of patients seen at our tertiary care centres. The Canadian Database of Osteoporosis and Osteopenia (CANDOO), a prospective observational database designed to capture clinical data, was searched for patients who started therapy following entry into CANDOO. There were 1196 initiating etidronate, 477 alendronate and 294 hormone replacement therapy women and men aged (mean, SD) 65.8 (8.7) years in the study. A Cox proportional hazards regression model was used to assess differences between treatment groups in the time to discontinuation of therapy. Several potential covariates such as anthropometry, medications, illnesses, fractures and lifestyle factors were entered into the model. A forward selection technique was used to generate the final model. Hazard ratios and 95% confidence intervals (CI) were calculated. Adjusted results indicated that alendronate-treated patients were more likely to discontinue therapy as compared with etidronate-treated patients (1.404; 95% CI: 1.150, 1.714). After 1 year, 90.3% of patients were still taking etidronate compared with 77.6% for alendronate. No statistically significant differences were found between hormone replacement therapy and etidronate users (0.971; 95% CI: 0.862, 1.093) and hormone replacement therapy and alendronate users (0.824; 95% CI: 0.624, 1.088) after controlling for potential covariates. After 1 year, 80.1% of patients were still taking hormone replacement therapy, which decreased to 44.5% after 6 years. Increasing age and presence of incident non-vertebral fractures were found to be independent predictors of adherence. In conclusion, alendronate users were more likely to discontinue therapy than etidronate users over the follow-up period. Potential barriers to long-term patient adherence to osteoporosis therapies need to be evaluated.

Aged↗
PubMed2003

Efficacy and safety of human parathyroid hormone-(1-84) in increasing bone mineral density in postmenopausal osteoporosis.

Daily sc injections of N-terminal analogs of PTH increase bone mass and decrease fractures in osteoporotic women. We investigated the efficacy and safety of human PTH-(1-84) (full-length PTH) in the treatment of postmenopausal osteoporosis in a double-blind, placebo-controlled study. The women (n = 50-53/group) self-administered PTH (50, 75, or 100 microg) or placebo by daily sc injection for 12 months. PTH treatment induced time- and dose-related increases in lumbar spine bone mineral density (BMD). The 100-microg dose increased BMD significantly at 3 months (+2.0%) and 12 months (+7.8%). BMD underestimated the anabolic effect of PTH in lumbar spine (bone mineral content, +10.0%) because bone area increased significantly (+2.0%). A nonsignificant decrease (-0.9%) in total hip BMD occurred during the first 6 months with the 100-microg dose, but this trend reversed (+1.6%) during the second 6 months. Bone turnover markers increased during the first half of the study and were maintained at elevated levels during the second 6 months. Protocol compliance was excellent (95-98%), and treatment was generally safe and well tolerated. Dose-related incidences of transient hypercalcemia occurred, but only one patient (100-microg group) was withdrawn because of repeated hypercalcemia. Thus, full-length PTH was efficacious and safe over 12 months.

Absorptiometry, Photon↗
PubMed2003

What predicts early fracture or bone loss on bisphosphonate therapy?

Factors predicting early fracture or bone loss on bisphosphonate therapy are not well defined. We studied 1588 patients over the age of 50 yr who were started on cyclic etidronate (1119) or alendronate (469) in the CANDOO (Canadian Database for Osteoporosis and Osteopenia Patients) Study. Incident fracture within 2 yr of starting therapy occurred in 31 patients and was independently predicted by a previous history of nonvertebral fracture (odds ratio [OR], 2.98, 95% confidence interval [CI], 1.30, 6.83, p = 0.010). Two hundred and fifty-seven patients lost >/=3% bone mass at the hip or spine (early bone loss) while on bisphosphonate therapy. Protection from early bone loss was most strongly independently predicted by treatment with alendronate with no previous history of etidronate use (OR, 0.29, CI, 0.13, 0.62, p = 0.002). In conclusion, early fracture on bisphosphonate therapy is most strongly predicted by a previous history of fracture and early bone loss is most strongly predicted by the potency of the prescribed bisphosphonate.

Alendronate↗
PubMed2002

Vitamin D insufficiency in a population of healthy western Canadians.

BACKGROUND: People with low levels of vitamin D and its metabolites are at increased risk for osteoporotic fractures. We wished to ascertain levels of vitamin D in a representative sample of adult western Canadians, to help assess the level of risk. We evaluated the prevalence of vitamin D insufficiency, defined as 25-hydroxyvitamin D [25(OH)D] less than 40 nmol/L, and seasonal variations in 25(OH)D, parathyroid hormone and related biochemical indices in a community-dwelling population of healthy Canadians living in Calgary (latitude 51 degrees 07'N). METHODS: During calendar year 1999, we collected fasting overnight blood samples every 3 months from 60 men and 128 women (age range 27 to 89 years) who had volunteered to participate in another study. We used commercial radioimmunoassay kits to measure calciotrophic hormones and other biochemical indices. Regression models for longitudinal data were used to assess the effect of season and other potential predictors on individual parameters. RESULTS: For a total of 64 participants (34%), vitamin D insufficiency, defined as 25(OH)D less than 40 nmol/L, was recorded at least once out of the 4 sampling times. After adjustment for age, body mass index and holiday travel, we observed the anticipated rise in serum 25(OH)D from a mean of 57.3 (standard deviation [SD] 21.3) nmol/L in the winter to 62.9 (SD 28.8) nmol/L in spring (p = 0.001) and 71.6 (SD 23.6) nmol/L in summer (p < 0.001), with a subsequent decline to 52.9 (SD 17.2) nmol/L in the fall (p = 0.008). The anticipated inverse relation between 25(OH)D and parathyroid hormone was not consistently observed: after adjustment for age, sex, body mass index and serum calcium, serum levels of parathyroid hormone did decrease significantly, from 39.5 (SD 18.8) ng/L in winter to 36.3 (SD 17.8) ng/L in summer (p = 0.001), but they continued to decline to 34.5 (SD 17.3) ng/L in the fall (p < 0.001). There was no association between 25(OH)D and parathyroid hormone (p = 0.21). INTERPRETATION: We documented a high prevalence of vitamin D insufficiency, which warrants consideration of dietary vitamin D supplementation.

Adult↗
PubMed2002

The impact of incident vertebral and non-vertebral fractures on health related quality of life in postmenopausal women.

BACKGROUND: Little empirical research has examined the multiple consequences of osteoporosis on quality of life. METHODS: Health related quality of life (HRQL) was examined in relationship to incident fractures in 2009 postmenopausal women 50 years and older who were seen in consultation at our tertiary care, university teaching hospital-affiliated office and who were registered in the Canadian Database of Osteoporosis and Osteopenia (CANDOO) patients. Patients were divided into three study groups according to incident fracture status: vertebral fractures, non-vertebral fractures and no fractures. Baseline assessments of anthropometric data, medical history, therapeutic drug use, and prevalent fracture status were obtained from all participants. The disease-targeted mini-Osteoporosis Quality of Life Questionnaire (mini-OQLQ) was used to measure HRQL. RESULTS: Multiple regression analyses revealed that subjects who had experienced an incident vertebral fracture had lower HRQL difference scores as compared with non-fractured participants in total score (-0.86; 95% confidence intervals (CI): -1.30, -0.43) and the symptoms (-0.76; 95% CI: -1.23, -0.30), physical functioning (-1.12; 95% CI: -1.57, -0.67), emotional functioning (-1.06; 95% CI: -1.44, -0.68), activities of daily living (-1.47; 95% CI: -1.97, -0.96), and leisure (-0.92; 95% CI: -1.37, -0.47) domains of the mini-OQLQ. Patients who experienced an incident non-vertebral fracture had lower HRQL difference scores as compared with non-fractured participants in total score (-0.47; 95% CI: -0.70, -0.25), and the symptoms (-0.25; 95% CI: -0.49, -0.01), physical functioning (-0.39; 95% CI: -0.65, -0.14), emotional functioning (-0.97; 95% CI: -1.20, -0.75) and the activities of daily living (-0.47; 95% CI: -0.73, -0.21) domains. CONCLUSION: Quality of life decreased in patients who sustained incident vertebral and non-vertebral fractures.

Journal Article↗
PubMed2002

Identification and functional characterization of novel calcium-sensing receptor mutations in familial hypocalciuric hypercalcemia and autosomal dominant hypocalcemia.

Familial hypocalciuric hypercalcemia (FHH), neonatal severe hyperparathyroidism (NSHPT), and autosomal dominant hypocalcemia (ADH), in which calcium homeostasis is disordered, are associated with mutations in the calcium-sensing receptor (CASR). Six unrelated kindreds with FHH and/or NSHPT and two unrelated kindreds with ADH were studied. Direct sequence analysis of the exons of the CASR gene identified heterozygous mutations in six of the kindreds with FHH and in one of those with ADH. We performed functional analyses on the novel missense and insertion/frameshift mutants by transiently transfecting wild-type and mutant CASRs tagged with a c-Myc epitope in human embryonic kidney (HEK293) cells. All mutant receptors were expressed at a similar level to that of the wild type; however, whereas mutants R220W and A835T (the ADH mutant) were fully glycosylated and were visualized on the cell surface, glycosylation of mutants G549R and C850-851 ins/fs was impaired, resulting in reduced cell surface staining. In fura-2-loaded HEK293 cells expressing the wild-type or mutant receptors, the inactivating R220W mutant produced a significant shift to the right relative to the wild-type CASR in the cytosolic calcium response to increasing extracellular calcium concentrations and the G549R and C850-851 ins/fs mutants were without detectable activity. The activating A835T mutation resulted in a shift to the left in the cytosolic calcium response to extracellular calcium concentrations relative to the wild type. Our studies have identified novel CASR mutations that alter the function of the CASR in several different ways.

Calcium↗
PubMedDate not supplied

Is there regional variation in the SF-36 scores of Canadian adults?

BACKGROUND: Canadian normative data for the Medical Outcomes Study 36-item short form (SF-36) have recently been published. However, there is evidence from other countries to suggest that regional variation in health-related quality of life (HRQOL) may exist. We therefore examined the SF-36 data from nine Canadian centres for evidence of systematic differences. METHODS: Bayesian hierarchical modelling was used to compare the differences in the eight SF-36 domains and the two summary component scores within each of the age and gender strata across the nine sites. RESULTS: Five domains and the two summary component scores showed little clinically important variation. Other than a small number of exceptions, there was little overall evidence of HRQOL differences across most domains and across most sites. INTERPRETATION: Our finding of only a few small differences suggests that there is no need to develop region-specific Canadian normative data for the SF-36 health survey.

Adult↗
PubMedDate not supplied

Stability of normative data for the SF-36: results of a three-year prospective study in middle-aged Canadians.

BACKGROUND: The SF-36 is widely used to assess health-related quality of life (HRQOL), but with few longitudinal studies in healthy populations, it is difficult to quantify its natural history. This is important because any measure of change following an intervention may be confounded by natural changes in HRQOL. This paper assesses mean changes in SF-36 scores over a 3-year period in men and women between the ages of 40 and 59 years at baseline. METHODS: Subjects were randomly selected from nine Canadian cities. Mean SF-36 changes over a 3-year period (1996/1997-1999/2000) were calculated for each gender within 5-year age categories. Multiple imputation was used to correct for potential bias due to missing data. RESULTS: The baseline cohort included 1,974 women and 975 men between 40 and 59 years. Mean changes in HRQOL tended to be small. Women demonstrated small average declines in 22 of the 32 age and domain groupings (4 age groups, 8 SF-36 domains) while men showed declines in 14/32. Most participants stayed within 10 points of their original baseline score. INTERPRETATION: Mean SF-36 scores change only slightly over three years in middle-aged Canadians, although there is much individual variation. It may be necessary to adjust for the natural evolution of SF-36 scores when interpreting results from longitudinal studies.

Age Distribution↗