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1.  Fractures are increased and bisphosphonate use decreased in individuals with insulin-dependent diabetes: a 10 year cohort study 
Background
Individuals with diabetes have been found previously to be at increased risk of non-traumatic fracture. However, it is unclear if these individuals are being identified and treated for osteoporosis.
Methods
7753 Canadians over 50 years of age were followed prospectively for 10 years. 606/7753 (7.8%) of had diabetes; 98 were insulin-dependent and 508 were not. Using a cox proportional hazards model, we assessed the association between diabetes status and incident non-traumatic fracture. Using logistic regression we identified factors associated with bisphosphonate use over the 10 year period of study.
Results
Mean (SD) age of participants was 66.7(9.4) years and 72% were female. Those with diabetes had higher BMD T-scores at baseline, with a mean (SD) femoral neck T-Score of -0.97 (1.06), compared to -1.24 (0.99) in the general cohort. The adjusted hazard ratio (HR) for incident non-traumatic fracture in individuals with insulin-dependent diabetes over the 10 year study period was 2.50 (95% confidence interval [CI] 1.60, 3.90; p < 0.001). Despite this increased fracture rate, individuals with diabetes (insulin-dependent or non-insulin-dependent) were less likely to be on bisphosphonate therapy at any point over 10 years of prospective follow up compared to other CaMos subjects (odds ratio [OR]: 0.59; 95% CI 0.46-0.75, p < 0.001).
Conclusions
Despite the increased risk of non-traumatic fracture associated with insulin-dependent diabetes, we that found individuals with diabetes are less likely to be treated with a bisphosphonate than those without diabetes. These findings point to a possible care gap in the treatment of non-traumatic fractures in individuals with diabetes in Canada.
doi:10.1186/1471-2474-15-201
PMCID: PMC4065314  PMID: 24919660
Fracture; Diabetes; Insulin; Care gap; Treatment; Osteoporosis
2.  Frailty index of deficit accumulation and falls: data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) Hamilton cohort 
Background
To investigate the association between frailty index (FI) of deficit accumulation and risk of falls, fractures, death and overnight hospitalizations in women aged 55 years and older.
Methods
The data were from the Global Longitudinal Study of Osteoporosis in Women (GLOW) Hamilton Cohort. In this 3-year longitudinal, observational cohort study, women (N = 3,985) aged ≥55 years were enrolled between May 2008 and March 2009 in Hamilton, Canada. A FI including co-morbidities, activities of daily living, symptoms and signs, and healthcare utilization was constructed using 34 health deficits at baseline. Relationship between the FI and falls, fractures, death and overnight hospitalizations was examined.
Results
The FI was significantly associated with age, with a mean rate of deficit accumulation across baseline age of 0.004 or 0.021 (on a log scale) per year. During the third year of follow-up, 1,068 (31.89%) women reported at least one fall. Each increment of 0.01 on the FI was associated with a significantly increased risk of falls during the third year of follow-up (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.02-1.03). The area under the curve (AUC) of the predictive model was 0.69 (95% CI: 0.67-0.71). Results of subgroup and sensitivity analyses indicated the relationship between the FI and risk of falls was robust, while bootstrap analysis judged its internal validation. The FI was significantly related to fractures (hazard ratio [HR]: 1.02, 95% CI: 1.01-1.03), death (OR: 1.05, 95% CI: 1.03-1.06) during the 3-year follow-up period and overnight hospitalizations (incidence rate ratio [IRR]: 1.02, 95% CI: 1.02-1.03) for an increase of 0.01 on the FI during the third year of follow-up. Measured by per standard deviation (SD) increment of the FI, the ORs were 1.21 and 1.40 for falls and death respectively, while the HR was 1.17 for fractures and the IRR was 1.18 for overnight hospitalizations respectively.
Conclusion
The FI of deficit accumulation increased with chronological age significantly. The FI was associated with and predicted increased risk of falls, fractures, death and overnight hospitalizations significantly.
doi:10.1186/1471-2474-15-185
PMCID: PMC4046442  PMID: 24885323
Frailty; Falls; Fracture; Death; Hospitalization
3.  The effect of regular physical activity on bone mineral density in post-menopausal women aged 75 and over: a retrospective analysis from the Canadian multicentre osteoporosis study 
Background
Physical activity is known to benefit many physiological processes, including bone turnover. There are; however, currently no clinical guidelines regarding the most appropriate type, intensity and duration of activity to prevent bone loss.
Methods
To help address this gap in the literature, we performed a retrospective analysis of data from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective cohort of 9423 adult patients, to determine the relationship between the amount of regular daily physical activity performed and bone mineral density. A total of 1169 female participants aged 75 and over provided information regarding their daily activity levels, including the amount of time spent each week performing physical activity at varying levels of intensity. Multiple and linear regression analyses were used to determine the effect of increasing amounts of this regular physical activity on bone mineral density.
Results
The results indicate that a step increase in the amount of physical activity performed each day resulted in a positive effect on bone mineral density at the hip, Ward’s triangle, trochanter and femoral neck (B = 0.006 to 0.008, p < 0.05). Possible confounding factors such as the use of anti-resorptive therapy, body mass index and age were included in the analysis and suggested that age had a negative effect on bone density while body mass index had a positive effect. Anti-resorptive therapy provided a protective effect against loss of bone density.
Conclusions
The data indicate that a step increase in the amount of daily activity, using simple, daily performed tasks, can help prevent decreases in post-menopausal bone mineral density.
doi:10.1186/1471-2474-14-253
PMCID: PMC3765292  PMID: 23971674
Osteoporosis; Physical activity; Bone mineral density; Post-menopausal
4.  Changes in trabecular bone microarchitecture in postmenopausal women with and without type 2 diabetes: a two year longitudinal study 
Background
The risk of experiencing an osteoporotic fracture is greater for adults with type 2 diabetes despite higher than normal bone mineral density (BMD). In addition to BMD, trabecular bone microarchitecture contributes to bone strength, but is not assessed using conventional BMD measurement by dual x-ray absorptiometry (DXA). The aim of this study was to compare two year changes in trabecular bone microarchitecture in women with and without type 2 diabetes.
Methods
We used a 1 Tesla magnetic resonance imaging (MRI) scanner to acquire axial images (resolution 195 μm × 195 μm × 1000 μm) of the distal radius. We report the change in the number and size of trabecular bone holes, bone volume fraction (BVTV), trabecular thickness (Tb.Th), number (Tb.N) and separation (Tb.Sp), endosteal area, nodal and branch density for each group. Lumbar spine and proximal femur BMD were measured with DXA (Hologic, Discovery QDR4500A) at baseline and follow-up. Using a multivariable linear regression model, we evaluated whether the percent change in the trabecular bone microarchitecture variables differed between women with and without type 2 diabetes.
Results
Of the 54 participants at baseline with valid MRI image sets, 37 participants (baseline mean [SD] age, 70.8 [4.4] years) returned for follow-up assessment after 25.4 [1.9] months. Lumbar spine BMD was greater for women with diabetes compared to without diabetes at both baseline and follow-up. After adjustment for ethnicity, women with diabetes had a higher percent increase in number of trabecular bone holes compared to controls (10[1] % versus −7 [2]%, p=0.010), however results were no longer significant after adjustment for multiple comparisons (p=0.090). There were no differences in the change in other trabecular bone microarchitecture variables between groups.
Conclusion
There were no differences in percent change in trabecular bone microarchitecture variables over two years in women with type 2 diabetes compared to women without diabetes. This study provides feasibility data, which will inform future trials assessing change in trabecular bone microarchitecture in women with type 2 diabetes. Larger studies using higher resolution imaging modalities that can assess change in trabecular and cortical bone compartments in women with type 2 diabetes are needed.
doi:10.1186/1471-2474-14-114
PMCID: PMC3618189  PMID: 23530948
5.  Surgical preferences of patients at risk of hip fractures: hemiarthroplasty versus total hip arthroplasty 
Background
The optimal treatment of displaced femoral neck fractures in patients over 60 years is controversial. While much research has focused on the impact of total hip arthroplasty (THA) and hemiarthroplasty (HA) on surgical outcomes, little is known about patient preferences for either alternative. The purpose of this study was to elicit surgical preferences of patients at risk of sustaining hip fracture using a novel decision board.
Methods
We developed a decision board for the surgical management of displaced femoral neck fractures presenting risks and outcomes of HA and THA. The decision board was presented to 81 elderly patients at risk for developing femoral neck fractures identified from an osteoporosis clinic. The participants were faced with the scenario of sustaining a displaced femoral neck fracture and were asked to state their treatment option preference and rationale for operative procedure.
Results
Eighty-five percent (85%) of participants were between the age of 60 and 80 years; 89% were female; 88% were Caucasian; and 49% had some post-secondary education. Ninety-three percent (93%; 95% confidence interval [CI], 87-99%) of participants chose THA as their preferred operative choice. Participants identified several factors important to their decision, including the perception of greater walking distance (63%), less residual pain (29%), less reoperative risk (28%) and lower mortality risk (20%) with THA. Participants who preferred HA (7%; 95% CI, 1-13%) did so for perceived less invasiveness (50%), lower dislocation risk (33%), lower infection risk (33%), and shorter operative time (17%).
Conclusion
The overwhelming majority of patients preferred THA to HA for the treatment of a displaced femoral neck fracture when confronted with risks and outcomes of both procedures on a decision board.
doi:10.1186/1471-2474-12-289
PMCID: PMC3280185  PMID: 22196211
6.  The relative efficacy of nine osteoporosis medications for reducing the rate of fractures in post-menopausal women 
Background
In the absence of head-to-head trials, indirect comparisons of randomized placebo-controlled trials may provide a viable option to assess relative efficacy. The purpose was to estimate the relative efficacy of reduction of fractures in post-menopausal women, and to assess robustness of the results.
Methods
A systematic literature review of multiple databases identified randomized placebo-controlled trials with nine drugs for post-menopausal women. Odds ratio and 95% credibility intervals for the rates of hip, non-vertebral, vertebral, and wrist fractures for each drug and between drugs were derived using a Bayesian approach. A drug was ranked as the most efficacious if it had the highest posterior odds ratio, or had the highest effect size.
Results
30 studies including 59,209 patients reported fracture rates for nine drugs: alendronate (6 studies), denosumab (1 study), etidronate (8 studies), ibandronate (4 studies), raloxifene (1 study), risedronate (7 studies), strontium (2 study), teriparatide (1 study), and zoledronic acid (1 study). The drugs with the highest probability of reducing non-vertebral fractures was etidronate and teriparatide while the drugs with the highest probability of reducing vertebral, hip or wrist fractures were teriparatide, zoledronic acid and denosumab. The drugs with the largest effect size for vertebral fractures were zoledronic acid, teriparatide and denosumab, while the drugs with the highest effect size for non-vertebral, hip or wrist fractures were alendronate or risedronate. Estimates were consistent between Bayesian and classical approaches.
Conclusion
Teriparatide, zoledronic acid and denosumab have the highest probabilities of being most efficacious for non-vertebral and vertebral fractures, and having the greatest effect sizes. The estimates from indirect comparisons were robust to differences in methodology.
doi:10.1186/1471-2474-12-209
PMCID: PMC3196921  PMID: 21943363
7.  A randomized controlled trial of vitamin D dosing strategies after acute hip fracture: No advantage of loading doses over daily supplementation 
Background
There remains uncertainty regarding the appropriate therapeutic management of hip fracture patients. The primary aim of our study was to examine whether large loading doses in addition to daily vitamin D offered any advantage over a simple daily low-dose vitamin D regimen for increasing vitamin D levels.
Methods
In this randomized controlled study, patients over age 50 with an acute fragility hip fracture were enrolled from two hospital sites in Ontario, Canada. Participants were randomized to one of three loading dose groups: placebo; 50,000 IU vitamin D2; or 100,000 IU D2. Following a placebo/loading dose, all patients received a daily tablet of 1,000 IU vitamin D3 for 90 days. Serum 25-hydroxy vitamin D (25-OHD) was measured at baseline, discharge from acute care (approximately 4-weeks), and 3-months.
Results
Sixty-five patients were enrolled in the study (44% male). An immediate rise in 25-OHD occurred in the 100,000 group, however there were no significant differences in 25-OHD between the placebo, 50,000 and 100,000 loading dose groups after 4-weeks (69.3, 84.5, 75.6 nmol/L, p = 0.15) and 3-months (86.7, 84.2, 73.3 nmol/L, p = 0.09), respectively. At the end of the study, approximately 75% of the placebo and 50,000 groups had reached the target therapeutic range (75 nmol/L), and 44% of the 100,000 group.
Conclusions
In correcting vitamin D insufficiency/deficiency in elderly patients with hip fracture, our findings suggest that starting with a lower daily dose of Vitamin D3 achieved similar results as providing an additional large loading dose of Vitamin D2. At the end of the study, all three groups were equally effective in attaining improvement in 25-OHD levels. Given that a daily dose of 1,000 IU vitamin D3 (with or without a loading dose) resulted in at least 25% of patients having suboptimal vitamin D status, patients with acute hip fracture may benefit from a higher daily dose of vitamin D.
Trial registration
Clinical Trials # NCT00424619
doi:10.1186/1471-2474-12-135
PMCID: PMC3134427  PMID: 21689448
8.  Safety of bazedoxifene in a randomized, double-blind, placebo- and active-controlled phase 3 study of postmenopausal women with osteoporosis 
Background
We report the safety findings from a 3-year phase 3 study (NCT00205777) of bazedoxifene, a novel selective estrogen receptor modulator under development for the prevention and treatment of postmenopausal osteoporosis.
Methods
Healthy postmenopausal osteoporotic women (N = 7,492; mean age, 66.4 years) were randomized to daily doses of bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo for 3 years. Safety and tolerability were assessed by adverse event (AE) reporting and routine physical, gynecologic, and breast examination.
Results
Overall, the incidence of AEs, serious AEs, and discontinuations due to AEs in the bazedoxifene groups was not different from that seen in the placebo group. The incidence of hot flushes and leg cramps was higher with bazedoxifene or raloxifene compared with placebo. The rates of cardiac disorders and cerebrovascular events were low and evenly distributed among groups. Venous thromboembolic events, primarily deep vein thromboses, were more frequently reported in the active treatment groups compared with the placebo group; rates were similar with bazedoxifene and raloxifene. Bazedoxifene showed a neutral effect on the breast and an excellent endometrial safety profile. The incidence of fibrocystic breast disease was lower with bazedoxifene 20 and 40 mg versus raloxifene or placebo. Reductions in total and low-density lipoprotein levels and increases in high-density lipoprotein levels were seen with bazedoxifene versus placebo; similar results were seen with raloxifene. Triglyceride levels were similar among groups.
Conclusion
Bazedoxifene showed a favorable safety and tolerability profile in women with postmenopausal osteoporosis.
Trial Registration
Trial registration number: NCT00205777; Trial registration date: September 16, 2005
doi:10.1186/1471-2474-11-130
PMCID: PMC2908075  PMID: 20569451
9.  Adverse events, bone mineral density and discontinuation associated with generic alendronate among postmenopausal women previously tolerant of brand alendronate: a retrospective cohort study 
Background
A rise in gastrointestinal (GI) adverse events (AEs) and a decline in bone mineral density (BMD) was observed in patients previously tolerant to brand alendronate shortly after generic versions were introduced in July 2005 to the Canadian market. The objective of our study was to quantify changes in AE rates and BMD scores, as well as associated alendronate discontinuation among patients before and after switch from brand to generic alendronate.
Methods
A chart review of postmenopausal women 50 years of age and older between 2003 and 2007 was conducted in two specialized tertiary care referral centers. Patients on alendronate both before and after July 2005 were included. The change in the number of AEs, changes in BMD and associated alendronate discontinuation was compared before and after the switch from brand to generic alendronate.
Results
301 women with an average age of 67.6 years (standard deviation (SD) = 9.5) had a total of 47 AEs between July 2003 and December 2007 that resulted in discontinuation of the medication. There was a significant increase in the rate of AEs per patient-months-at-risk from 0.0001 before to 0.0044 after October 2005 (p < 0.001). The most common AEs were GI in nature (stomach pain, GI upset, nausea, and reflux). In addition, 23 patients discontinued alendronate due to BMD reduction after January 2006. In these patients, BMD scores were significantly reduced from their prior BMD measures (change of -0.0534, p < 0.001 for spine BMD and change of -0.0338, p = 0.01 for femur BMD). Among patients who discontinued due to BMD reduction, BMD was stable in the period prior to January 2006 (change of -0.0066, p = 0.5 for spine BMD and change of 0.0011, p = 0.9 for femur BMD); however, testing for reduction after January 2006 in BMD measures (one-sided T-test) revealed there was a significant reduction in BMD scores for both anatomic sites (change of -0.0321, p = .005 for spine, change of -0.0205, p = 0.05 for femur).
Conclusions
Patients who were previously stable on doses of brand alendronate experienced an increase in AEs causing discontinuation after introduction of automatic substitution to generic alendronate. In addition, reductions in BMD were observed in some patients who had stable BMDs before January 2006. Given the substantial increase in AEs, generic alendronate may not be as well tolerated as brand alendronate.
doi:10.1186/1471-2474-11-68
PMCID: PMC2867835  PMID: 20388226
10.  Improvement in health-related quality of life in osteoporosis patients treated with teriparatide 
Background
Individuals with osteoporosis and recent vertebral fractures suffer from pain and impaired health-related quality of life (HRQL). To determine whether patients with osteoporosis treated with teriparatide experienced improvement in HRQL and pain symptoms after several months of therapy.
Methods
We retrospectively studied a sample of osteoporosis patients treated with teriparatide in a Canadian rheumatology practice. We included patients that received teriparatide therapy with baseline and follow-up Mini-Osteoporosis Quality of Life Questionnaire (OQLQ) data. Follow-up data was measured at three or six months. We used a paired Student's t-test to compare baseline and follow-up measurements for each of the questionnaire's ten questions (five domains). Statistical analysis was also repeated to only include patients who suffered a prior vertebral fracture.
Results
57 patients were included in the study, including 47 women. The mean age was 63.8 years (standard deviation 12.1 years). About sixty five percent (37/57) had previously sustained one or more osteoporotic fractures and about 38.6% (22/57) had suffered a prior vertebral fracture. About 44% (25/57) of individuals were taking one or more types of pain medications regularly prior to starting therapy. At follow-up, significant improvements were observed in the OQLQ domains of pain symptoms. This was seen when all patients on teriparatide were included, and also when only patients with prior vertebral fractures were included. There was also an improvement in emotional functioning, relating to fear of falling at 3 months follow-up (p = 0.019). Respondents also reported improvement in the domain of activities of daily living, relating to vacuuming at 6 months follow-up (p = 0.036), and an improvement in the leisure domain, relating to ease of traveling in the prior vertebral fracture population at 3 months follow-up (p = 0.012). However, there was no significant improvement observed in the domains of physical functioning. Participants also reported a decrease in need for pain medications, with 26% (15/57) requiring analgesics at the time of follow-up.
Conclusion
Teriparatide use may be associated with improvements in HRQL in osteoporosis patients, in particular alleviation of pain symptoms. These results were especially evident in patients with a history of vertebral fractures. These findings should be confirmed in larger prospective studies with a suitable control group.
doi:10.1186/1471-2474-9-151
PMCID: PMC2588585  PMID: 18990249
11.  Optimizing care in osteoporosis: The Canadian quality circle project 
Background
While the Osteoporosis Canada 2002 Canadian guidelines provided evidence based strategies in preventing, diagnosing, and managing this condition, publication and distribution of guidelines have not, in and of themselves, been shown to alter physicians clinical approaches. We hypothesize that primary care physicians enrolled in the Quality Circle project would change their patient management of osteoporosis in terms of awareness of osteoporosis risk factors and bone mineral density testing in accordance with the guidelines.
Methods
The project consisted of five Quality Circle phases that included: 1) Training & Baseline Data Collection, 2) First Educational Intervention & First Follow-Up Data Collection 3) First Strategy Implementation Session, 4) Final Educational Intervention & Final Follow-up Data Collection, and 5) Final Strategy Implementation Session. A total of 340 circle members formed 34 quality circles and participated in the study. The generalized estimating equations approach was used to model physician awareness of risk factors for osteoporosis and appropriate utilization of bone mineral density testing pre and post educational intervention (first year of the study). Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated.
Results
After the 1st year of the study, physicians' certainty of their patients' risk factor status increased. Certainty varied from an OR of 1.4 (95% CI: 1.1, 1.8) for prior vertebral fracture status to 6.3 (95% CI: 2.3, 17.9) for prior hip fracture status. Furthermore, bone mineral density testing increased in high risk as compared with low risk patients (OR: 1.4; 95% CI: 1.2, 1.7).
Conclusion
Quality Circle methodology was successful in increasing both physicians' awareness of osteoporosis risk factors and appropriate bone mineral density testing in accordance with the 2002 Canadian guidelines.
doi:10.1186/1471-2474-9-130
PMCID: PMC2567974  PMID: 18828906
12.  Longitudinal analysis of vertebral fracture and BMD in a Canadian cohort of adult cystic fibrosis patients 
Background
Vertebral fractures in patients with cystic fibrosis (CF) may contribute to an accelerated decline in lung function and can be a contraindication to lung transplantation. In this study, we examined longitudinal change in bone mineral density (BMD) and the prevalence of vertebral fractures in adult CF patients, without lung-transplant, attending a Canadian specialty clinic.
Methods
Retrospective chart review of all patients attending an Adult Cystic Fibrosis Clinic at Hamilton Health Sciences in Hamilton, Canada. Forty-nine of 56 adults met inclusion criteria. Chest radiographs were graded by consensus approach using Genant's semi-quantitative method to identify and grade fractured vertebrae. Dual x-ray absorptiometry (DXA) scans were also reviewed.
Results
The mean age of the cohort was 25.2 years (SD 9.4), 43% were male. The mean body mass index (BMI) was 19.8 (2.8) for males and 21.7 (5.1) for females. At baseline, the rate of at least one vertebral fracture was 16.3%; rising to 21.3% (prevalent and incident) after a 3-year follow-up. The mean BMD T-or Z-scores at baseline were -0.80 (SD 1.1) at the lumbar spine, -0.57 (SD 0.97) at the proximal femur, and -0.71 (SD 1.1) at the whole body. Over approximately 4-years, the mean percent change in BMD was -1.93% at the proximal femur and -0.73% at the lumbar spine.
Conclusion
Approximately one in five CF patients demonstrated at least one or more vertebral fractures. Moderate declines in BMD were observed. Given the high rate of vertebral fractures noted in this cohort of adult CF patients, and the negative impact they have on compromised lung functioning, regular screening for vertebral fractures should be considered on routine chest radiographs.
doi:10.1186/1471-2474-9-125
PMCID: PMC2567975  PMID: 18801200
13.  Minimum joint space width and tibial cartilage morphology in the knees of healthy individuals: A cross-sectional study 
Background
The clinical use of minimum joint space width (mJSW) and cartilage volume and thickness has been limited to the longitudinal measurement of disease progression (i.e. change over time) rather than the diagnosis of OA in which values are compared to a standard. This is primarily due to lack of establishment of normative values of joint space width and cartilage morphometry as has been done with bone density values in diagnosing osteoporosis. Thus, the purpose of this pilot study is to estimate reference values of medial joint space width and cartilage morphometry in healthy individuals of all ages using standard radiography and peripheral magnetic resonance imaging.
Design
For this cross-sectional study, healthy volunteers underwent a fixed-flexion knee X-ray and a peripheral MR (pMR) scan of the same knee using a 1T machine (ONI OrthOne™, Wilmington, MA). Radiographs were digitized and analyzed for medial mJSW using an automated algorithm. Only knees scoring ≤1 on the Kellgren-Lawrence scale (no radiographic evidence of knee OA) were included in the analyses. All 3D SPGRE fat-sat sagittal pMR scans were analyzed for medial tibial cartilage morphometry using a proprietary software program (Chondrometrics GmbH).
Results
Of 119 healthy participants, 73 were female and 47 were male; mean (SD) age 38.2 (13.2) years, mean BMI 25.0 (4.4) kg/m2. Minimum JSW values were calculated for each sex and decade of life. Analyses revealed mJSW did not significantly decrease with increasing decade (p > 0.05) in either sex. Females had a mean (SD) medial mJSW of 4.8 (0.7) mm compared to males with corresponding larger value of 5.7 (0.8) mm. Cartilage morphometry results showed similar trends with mean (SD) tibial cartilage volume and thickness in females of 1.50 (0.19) μL/mm2 and 1.45 (0.19) mm, respectively, and 1.77 (0.24) μL/mm2 and 1.71 (0.24) mm, respectively, in males.
Conclusion
These data suggest that medial mJSW values do not decrease with aging in healthy individuals but remain fairly constant throughout the lifespan with "healthy" values of 4.8 mm for females and 5.7 mm for males. Similar trends were seen for cartilage morphology. Results suggest there may be no need to differentiate a t-score and a z-score in OA diagnosis because cartilage thickness and JSW remain constant throughout life in the absence of OA.
doi:10.1186/1471-2474-9-119
PMCID: PMC2542509  PMID: 18778479
14.  Do patients perceive a link between a fragility fracture and osteoporosis? 
Background
To evaluate factors associated with whether patients associate their fracture with future fracture risk.
Methods
Fragility fracture patients participated in a telephone interview. Unadjusted odds ratios (OR, [95% CI]) were calculated to identify factors associated with whether patients associate their fracture with increased fracture risk or osteoporosis. Predictors identified in univariate analysis were entered into multivariable logistic regression models.
Results
127 fragility fracture patients (82% female) participated in the study, mean (SD) age 67.5 (12.7) years. An osteoporosis diagnosis was reported in 56 (44%) participants, but only 17% thought their fracture was related to osteoporosis. Less than 50% perceived themselves at increased risk of fracture. The odds of an individual perceiving themselves at increased risk for fracture were higher for those that reported a diagnosis of osteoporosis (OR 22.91 [95%CI 7.45;70.44], p < 0.001), but the odds decreased with increasing age (0.95 [0.91;0.99], p<0.009). The only variable significantly associated with the perception that the fracture was related to osteoporosis was self-reported osteoporosis diagnosis (39.83 [8.15;194.71], p<0.001).
Conclusion
Many fragility fracture patients do not associate their fracture with osteoporosis. It is crucial for physicians to communicate to patients that an osteoporosis diagnosis, increasing age or a fragility fracture increases the risk for future fracture.
doi:10.1186/1471-2474-9-38
PMCID: PMC2329635  PMID: 18366716
15.  Evaluation of easily measured risk factors in the prediction of osteoporotic fractures 
Background
Fracture represents the single most important clinical event in patients with osteoporosis, yet remains under-predicted. As few premonitory symptoms for fracture exist, it is of critical importance that physicians effectively and efficiently identify individuals at increased fracture risk.
Methods
Of 3426 postmenopausal women in CANDOO, 40, 158, 99, and 64 women developed a new hip, vertebral, wrist or rib fracture, respectively. Seven easily measured risk factors predictive of fracture in research trials were examined in clinical practice including: age (<65, 65–69, 70–74, 75–79, 80+ years), rising from a chair with arms (yes, no), weight (< 57, ≥ 57kg), maternal history of hip facture (yes, no), prior fracture after age 50 (yes, no), hip T-score (>-1, -1 to >-2.5, ≤-2.5), and current smoking status (yes, no). Multivariable logistic regression analysis was conducted.
Results
The inability to rise from a chair without the use of arms (3.58; 95% CI: 1.17, 10.93) was the most significant risk factor for new hip fracture. Notable risk factors for predicting new vertebral fractures were: low body weight (1.57; 95% CI: 1.04, 2.37), current smoking (1.95; 95% CI: 1.20, 3.18) and age between 75–79 years (1.96; 95% CI: 1.10, 3.51). New wrist fractures were significantly identified by low body weight (1.71, 95% CI: 1.01, 2.90) and prior fracture after 50 years (1.96; 95% CI: 1.19, 3.22). Predictors of new rib fractures include a maternal history of a hip facture (2.89; 95% CI: 1.04, 8.08) and a prior fracture after 50 years (2.16; 95% CI: 1.20, 3.87).
Conclusion
This study has shown that there exists a variety of predictors of future fracture, besides BMD, that can be easily assessed by a physician. The significance of each variable depends on the site of incident fracture. Of greatest interest is that an inability to rise from a chair is perhaps the most readily identifiable significant risk factor for hip fracture and can be easily incorporated into routine clinical practice.
doi:10.1186/1471-2474-6-47
PMCID: PMC1208898  PMID: 16143046
16.  Does Alendronate reduce the risk of fracture in men? A meta-analysis incorporating prior knowledge of anti-fracture efficacy in women 
Background
Alendronate has been found to reduce the risk of fractures in postmenopausal women as demonstrated in multiple randomized controlled trials enrolling thousands of women. Yet there is a paucity of such randomized controlled trials in osteoporotic men. Our objective was to systematically review the anti-fracture efficacy of alendronate in men with low bone mass or with a history of prevalent fracture(s) and incorporate prior knowledge of alendronate efficacy in women in the analysis.
Methods
We examined randomized controlled trials in men comparing the anti-fracture efficacy of alendronate to placebo or calcium or vitamin D, or any combination of these. Studies of men with secondary causes of osteoporosis other than hypogonadism were excluded. We searched the following electronic databases (without language restrictions) for potentially relevant citations: Medline, Medline in Process (1966-May 24/2004), and Embase (1996–2004). We also contacted the manufacturer of the drug in search of other relevant trials. Two reviewers independently identified two trials (including 375 men), which met all inclusion criteria. Data were abstracted by one reviewer and checked by another. Results of the male trials were pooled using Bayesian random effects models, incorporating prior information of anti-fracture efficacy from meta-analyses of women.
Results
The odds ratios of incident fractures in men (with 95% credibility intervals) with alendronate (10 mg daily) were: vertebral fractures, 0.44 (0.23, 0.83) and non-vertebral fractures, 0.60 (0.29, 1.44).
Conclusion
In conclusion, alendronate decreases the risk of vertebral fractures in men at risk. There is currently insufficient evidence of a statistically significant reduction of non-vertebral fractures, but the paucity of trials in men limit the statistical power to detect such an effect.
doi:10.1186/1471-2474-6-39
PMCID: PMC1182376  PMID: 16008835
17.  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.
doi:10.1186/1471-2474-3-11
PMCID: PMC107028  PMID: 11967146
18.  Effect of vitamin D on bone mineral density of elderly patients with osteoporosis responding poorly to bisphosphonates 
Background
Bisphosphonates are indicated in the prevention and treatment of osteoporosis. However, bone mineral density (BMD) continues to decline in up to 15% of bisphosphonate users. While randomized trials have evaluated the efficacy of concurrent bisphosphonates and vitamin D, the incremental benefit of vitamin D remains uncertain.
Methods
Using data from the Canadian Database of Osteoporosis and Osteopenia (CANDOO), we performed a 2-year observational cohort study. At baseline, all patients were prescribed a bisphosphonate and counseled on vitamin D supplementation. After one year, patients were divided into two groups based on their response to bisphosphonate treatment. Non-responders were prescribed vitamin D 1000 IU daily. Responders continued to receive counseling on vitamin D.
Results
Of 449 patients identified, 159 were non-responders to bisphosphonates. 94% of patients were women. The mean age of the entire cohort was 74.6 years (standard deviation = 5.6 years). In the cohort of non-responders, BMD at the lumbar spine increased 2.19% (p < 0.001) the year after vitamin D was prescribed compared to a decrease of 0.55% (p = 0.36) the year before. In the cohort of responders, lumbar spine BMD improved 1.45% (p = 0.014) the first year and 1.11% (p = 0.60) the second year. The difference between the two groups was statistically significant the first year (p < 0.001) but not the second (p = 0.60). Similar results were observed at the femoral neck but were not statistically significant.
Conclusion
In elderly patients with osteoporosis not responding to bisphosphonates, vitamin D 1000 IU daily may improve BMD at the lumbar spine.
doi:10.1186/1471-2474-3-6
PMCID: PMC65678  PMID: 11860614

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