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Unlabelled: We evaluated the characteristics of 1,142 women and men who attended Canadian osteoporosis clinics and had T-score < or = -2.0 and no prior fractures to determine the predictors of first clinical fracture. Greater age and failure to start osteoporosis drug treatment increased the risk of first clinical fracture., Introduction: Although risk factors for osteoporotic fractures are well-known, it is unclear which factors predict poor prognosis in patients with primary osteoporosis. The purpose of this study was to determine prognostic factors for first clinical fracture in patients with T-score < or = -2.0 and no previous clinical fracture., Methods: We examined prospectively collected data from 1,142 patients aged 40 and over in the Canadian Database of Osteoporosis and Osteopenia. We used prognosis methodology and performed survival analysis to determine factors that increase the risk of first clinical fracture., Results: Our inception cohort (mean age = 60.6 years, 91% females) had a cumulative fracture incidence of 5.1% (incidence rate: 2.53/100 person-years). Age and osteoporosis drug use predicted incident clinical fractures in multivariable regression analyses. The risk of first fracture increased by 3% per year. Failing to initiate osteoporosis treatment increased fracture risk by 2.4 times. In addition, low physical activity, high body mass index and low T-scores were found to predict fracture risk in certain patient subgroups using tree-structured survival analysis. These findings were robust and did not change with most sensitivity analyses., Conclusion: Age and osteoporosis drug treatment are the main prognostic predictors of first clinical fracture in patients with T-score < or = -2.0.

The prevalence of osteoporosis in men is higher than previously assumed; consequently, numerous therapies are being investigated to treat these patients. The Canadian Database of Osteoporosis and Osteopenia patients (CANDOO) was analyzed to examine changes in bone mineral density (BMD) in consecutively seen osteoporotic men administered alendronate, etidronate or no bone-active drugs (control) over 1 year. A total of 244 men attending six Canadian osteoporosis clinics were included in the study (42 alendronate, 102 etidronate and 100 control). Multiple imputation was used to model missing data to provide a more robust statistical model. The imputed datasets (five) were analyzed using multivariable linear regression to determine differences between groups in the percent change of lumbar spine (LS) and femoral neck (FN) BMD from baseline to 1 year. Differences in the percent change in BMD from baseline were most notable at the LS in favor of alendronate (4.3%; 95% CI: 2.1, 6.6 ) and etidronate (2.1%; 95% CI: 0.3, 4.0) therapy when compared with controls. At the LS, alendronate therapy led to significantly greater (2.2%; 95% CI: 0.2, 4.2) gains in BMD as compared to etidronate therapy. Compared to controls, there were no significant differences in FN BMD with alendronate (2.1%; 95% CI: -0.4, 4.7) or etidronate therapy (0.9%; 95% CI: -1.1, 2.8), nor were there significant differences between bisphosphonate groups (1.3%; 95% CI: -1.1, 3.6, in favor of alendronate). While both alendronate and etidronate significantly increased LS BMD in osteoporotic men after 1 year in real-world settings, alendronate therapy resulted in significantly superior gains in LS BMD. The effect of these two bisphosphonates on fractures and FN BMD in osteoporotic men is likely positive, but requires further study.

Objective: Breast cancer survivors with osteoporosis or osteopenia are commonly encountered in primary care and gynaecology practices. Our objective was to determine whether treatment with oral bisphosphonates (alendronate or cyclic etidronate) was more effective than calcium with vitamin D in improving lumbar spine bone mineral density (BMD) within one year in breast cancer survivors., Methods: Breast cancer survivors with at least one year of clinical follow-up were identified from the prospective observational Canadian Database of Osteoporosis and Osteopenia (CANDOO). Analysis of covariance was used to examine the effects of bisphosphonate therapy on change in lumbar spine BMD at one year compared with the effects of calcium with vitamin D (analysis adjusted for baseline L2-L4 BMD, current tamoxifen use, number of prevalent vertebral fractures [VFs], and time since diagnosis of breast cancer, and age)., Results: Eighteen patients took calcium and vitamin D, 25 took cyclic etidronate, and 27 took oral alendronate. Adjusted one-year BMD increases for alendronate and cyclic etidronate compared to calcium and vitamin D were as follows: alendronate 4.53% (95% confidence interval [CI] 1.26%, 7.81%, P = 0.008), and cyclic etidronate 1.85% (-1.55%, 5.25%, P = 0.280). BMD increases were significantly greater in patients with prevalent VF compared to those without VF (P = 0.025). In contrast, time since diagnosis of breast cancer was significantly associated with a decrease in BMD (P = 0.002). We were unable to detect any effect of current tamoxifen use, baseline lumbar spine BMD, or age on changes in BMD at one year., Conclusion: Treatment with alendronate was associated with significantly greater improvements in lumbar spine BMD within one year in breast cancer survivors when compared with treatment with cyclic etidronate or calcium and vitamin D.

A history of fracture and a low bone mineral density (BMD) are the strongest predictors of future osteoporotic fracture. This prospective cohort study assessed the impact of these two factors on treatment patterns in women undergoing their first BMD testing in a non-academic community setting. Successive women seen for first BMD testing at two testing centers completed a baseline questionnaire and a mailed 3-month follow-up questionnaire. Patients were grouped by history of fracture after age 20 years (present, absent) and by BMD result [osteoporosis (OP), osteopenia (OPN), normal BMD]. Thirty percent of 1144 patients at least 45 years old reported a history of fracture after age 20 years. They were no more likely than those without a history of fracture to be taking calcium (52% of total), vitamin D (31%), estrogen (31%), or a bisphosphonate (2%) before BMD testing. The BMD testing revealed OP in 20%, OPN in 45%, and normal BMD in 35%. Three months later, the percentages of patients taking treatments differed as follows: calcium (66 vs 53% in OP and OPN groups vs normal BMD), vitamin D (46 vs 37% in OPN group vs normal BMD), estrogen (25 vs 36 vs 44% in groups with OP, OPN, and normal BMD), a bisphosphonate (43 vs 11 vs 1%), and at least one of estrogen or a bisphosphonate (58 vs 43 vs 46%). Treatment decisions were influenced by first BMD testing but not significantly by a history of fracture. There is a substantial care gap in the treatment of patients with OP: either bisphosphonate or estrogen therapy was taken by only 31% of patients at least 45 years old and with a history of fracture after age 20 years before BMD testing and by only 58% of these and who also had OP by BMD.

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.

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.

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.

We investigated whether an increase in lumbar spine bone mineral density (LS BMD) at 6 months or at 12 months could predict the response to intermittent cyclical therapy (ICT) with etidronate, defined in one of two ways: (i) an increase in LS BMD at 24 months (improvement) or (ii) an increase in LS BMD > or = 0.028 g/cm2 (significant improvement). The latter is a precision term calculated from test-retest values for LS BMD in osteoporotic patients. Two hundred and forty-seven patients (32 men; 5 premenopausal and 210 postmenopausal women) were followed for 24 months by dual-energy X-ray absorptiometry (DXA) and were not taking estrogen, calcitonin or fluoride during treatment with ICT-etidronate. One hundred and fifty patients had a LS BMD measurement after 6 months of treatment with ICT-etidronate and 205 patients had one at 12 months. Baseline characteristics (mean;SD) were as follows: age, 66;11 years; years since menopause, 21;10; number of vertebral fractures at baseline, 0.87;1.26; LS BMD T-score, -2.8; 1.2. After 24 months of treatment with ICT-etidronate, 81% of the patients had an improvement, and 55% had a significant improvement at the LS. Only 6% significantly lost bone (loss of 0.028 g/cm2 or more). The mean percent change from baseline in LS BMD was 5.1% (95% confidence interval 4.2% to 6.0%). The results for men and postmenopausal women were similar to those for the entire group. Accuracy and sensitivity were marginally, but not significantly, higher when response was predicted using 12 month versus 6 month LS BMD measurements. The positive predictive values of improvement at 6 or 12 months were 89% and 90% respectively for improvement at 24 months, and 66% and 68% for significant improvement at 24 months. Identification of nonresponders was less successful and similar at 6 months and 12 months. Forty percent and 39% of the patients, who had no improvement at 6 or 12 months respectively, also had no improvement at 24 months, i.e., were true negatives, while 77% and 71% had no significant improvement at 24 months. The results may reflect slow response in a small subgroup of patients rather than nonresponse; however, no response at 1 year might identify patients whose rate of response is sufficiently slow that alternative therapy is justified. These data demonstrate a good response rate to ICT-etidronate and may help reduce the need for follow-up BMD measurements in those who show an early improvement.

Objective: To determine the longterm safety and efficacy of etidronate therapy in patients in whom corticosteroid induced bone loss has already occurred., Methods: We performed a 36 month observational cohort study in which all data were obtained from Canadian Database of Osteoporosis and Osteopenia (CANDOO) patients. The etidronate group consisted of 24 patients who received 400 mg of etidronate disodium for 14 days, followed by 76 days of calcium carbonate (500 mg of elemental calcium), repeated every 3 mo; the control group included 37 patients who received calcium carbonate 500 to 1000 mg daily. Outcome measurements included changes within groups from baseline and differences between groups in the bone mineral density (BMD) of the lumbar spine, femoral neck, and trochanter at 12, 24, and 36 months. The incidence of vertebral fractures was also determined., Results: Etidronate therapy resulted in a meaningful percentage increase from baseline in lumbar spine BMD, primarily during the first 24 months of treatment, and this increase was sustained for the remainder of the 36 month study period (5.2%; p = 0.016). Analysis of covariance revealed a significant percentage difference (SD) between groups in lumbar spine BMD at 12 [5.5 (13.5) percent; p = 0.003] and 24 months [6.0 (17.4) percent; p = 0.011] in favor of the etidronate group. After 3 years of therapy, one patient (4%) experienced one vertebral fracture in the etidronate group, whereas 3 patients (8%) experienced 5 vertebral fractures in the control group., Conclusion: Etidronate treatment administered for 36 months reversed lumbar spine bone loss, and appeared to be safe in patients with established corticosteroid induced osteoporosis.

The objectives were to determine the efficacy and safety of nasal salmon calcitonin 200 IU daily in the prevention of corticosteroid-induced osteoporosis. A minimized, double-blind, placebo-controlled trial was carried out in corticosteroid-treated patients with polymyalgia rheumatica. The setting was a tertiary care university-affiliated hospital and a total of 31 patients were enrolled. The primary outcome measure was the percentage change in bone mineral density of the lumbar spine in the two treatment groups from baseline to 1 yr of follow-up. The mean +/- S.D. bone mineral density of the lumbar spine in the calcitonin-treated group decreased by 1.29 +/- 6.76% and in the placebo group by 4.95 +/- 3.50% after 12 months. The observed difference of 3.65 +/- 2.10% between groups is statistically significant (P < 0.05). Nasal salmon calcitonin prevented loss of bone in the lumbar spine as measured by dual-energy X-ray absorptiometry.

Objective: To determine the efficacy and safety of vitamin D 50,000 units/week and calcium 1,000 mg/day in the prevention of corticosteroid induced osteoporosis., Methods: A minimized double blind, placebo controlled trial in corticosteroid treated subjects in a tertiary care university affiliated hospital. The sample was 62 subjects with polymyalgia rheumatica, temporal arteritis, asthma, vasculitis, or systemic lupus erythematosus. The primary outcome measure was the percentage change in bone mineral density (BMD) of the lumbar spine in the 2 treatment groups from baseline to 36 mo followup., Results: BMD of the lumbar spine in the vitamin D and calcium treated group decreased by a mean (SD) of 2.6% (4.1%) at 12 mo, 3.7% (4.5%) at 24 mo, and 2.2% (5.8%) at 36 mo. In the placebo group there was a decrease of 4.1% (4.1%) at 12 mo, 3.8% (5.6%) at 24 mo, and 1.5% (8.8%) at 36 mo. The observed differences between groups were not statistically significant. The difference at 36 mo was-0.693% (95% CI -5.34, 3.95)., Conclusion: Vitamin D and calcium may help prevent the early loss of bone seen in the lumbar spine as measured by densitometry of the lumbar spine. Longterm vitamin D and calcium in those undergoing extended therapy with corticosteroids does not appear to be beneficial.

The purpose of this study was to evaluate the efficacy of intermittent cyclic therapy (ICT) with etidronate in preventing the loss of lumbar vertebral bone mineral density (BMD) in patients taking corticosteroids. The study population was a cohort of patients taking corticosteroids for at least two years for polymyalgia rheumatica, asthma, rheumatoid arthritis, systemic lupus erythematosus or other conditions. A tertiary care university teaching hospital-affiliated rheumatology office practice. Inclusion and exclusion criteria yielded eighty-eight patients taking corticosteroids for at least two years who had not taken estrogen or fluoride and had no causes of secondary osteoporosis. Changes relative to baseline in individual vertebral (L2-L4) BMD measurements after one and two years were compared between patients who had taken ICT with etidronate (n = 42) and those who had not (n = 46). We found that BMD in the lumbar spine increased significantly over baseline in patients who had taken ICT with etidronate, by 3.9% after one year and by 5.6% after two years, whereas it decreased by 3.7-3.8% in patients who had not. We conclude that ICT with etidronate prevents corticosteroid-induced osteoporosis and progressively ameliorates BMD over two years. Double blind trials are underway to evaluate whether this increased BMD is associated with reductions in vertebral fracture rates.