Papers by Jonathan Adachi
Plos One, Dec 11, 2013
Objective: To examine when, where and how fractures occur in postmenopausal women.
Bone, 2015
Background: Population-based incident fracture data aid fracture prevention and therapy decisions... more Background: Population-based incident fracture data aid fracture prevention and therapy decisions. Our purpose was to describe 10-year site-specific cumulative fracture incidence by sex, age, and degree of trauma with/without consideration of competing mortality in the Canadian Multicentre Osteoporosis Study adult cohort. Methods: Incident fractures and mortality were identified by annual postal questionnaires to the participant or proxy respondent. Date, site and circumstance of fracture were gathered from structured interviews and medical records. Fracture analyses were stratified by sex and age and used both Kaplan-Meier and competing mortality methods. Results: The baseline (1995-97) cohort included 6314 women and 2789 men (aged 25-84 years; mean±SD 62±12 and 59±14, respectively), with 4322 (68%) women and 1732 (62%) men followed to Year-10. At least one incident fracture occurred for 930 women (14%) and 247 men (9%). Competing mortality exceeded fracture risk for men aged 65+ years at baseline. Age was a strong predictor of incident fractures especially fragility fractures, with higher age gradients for women vs. men. Major osteoporotic fracture (MOF) (hip, clinical spine, forearm, humerus) accounted for 41-74% of fracture risk by sex/age strata; in women all MOF sites showed agerelated increases but in men only hip was clearly age-related. The most common fractures were forearm for women and ribs for men. Hip fracture incidence was highest for the 75-84 year baseline age-group and was equal by sex: women 7.0% (95% CI 5.3, 8.9), men 7.0% (95% CI 4.4, 10.3). Interpretation: There are sex differences in the predominant sites and age-gradients of fracture. In older men, competing mortality exceeds cumulative fracture risk.
Archives of Osteoporosis, 2014
We determined the prospective 10-year association among incident fragility fractures and four glu... more We determined the prospective 10-year association among incident fragility fractures and four glucocorticoid (GC) treatment groups (Never GC, Prior GC, Baseline GC, and Ever GC). Results showed that GC treatment is associated with increased 10-year incident fracture risk in ambulatory men and women across Canada. Using the Canadian Multicentre Osteoporosis Study dataset, we determined the prospective 10-year association between incident fragility fractures and GC treatment. We conducted a 10-year prospective observational cohort study at nine sites across Canada. A total of 9,263 ambulatory men and women 25 years of age and older were included in the analysis. Multivariable Cox proportional hazards analyses were conducted to determine the relationship among GC treatment groups in four levels that included Never GC, Prior GC, Baseline GC, and Ever GC (combined baseline and prior groups) and time to fracture. In each of the Never GC, Prior GC, Baseline GC, and Ever GC treatment groups, the number of participants were 8,832 (95.4 %), 303 (3.3 %), 128 (1.4 %), and 431 (4.7 %), respectively. Of the 9,263 individuals enrolled, incident fragility non-spine, hip, spine, and any fractures were experienced by a total of 896 (9.67 %), 157 (1.69 %), 130 (1.40 %), and 1,102 (11.90 %) over 10-years, respectively. For men and women combined, prior GC treatment was associated with a higher hazard ratio (HR) for time to incident non-vertebral (HR = 1.5, 95 % confidence interval [CI] = 1.1, 2.0), hip (HR = 2.1, 95 % CI = 1.1, 4.0), and any fracture (HR = 1.4, 95 % CI = 1.0, 1.8) compared with never GC treatment. GC treatment is associated with increased 10-year incident fracture risk; this highlights the importance of considering therapy to prevent GC-induced fractures for patients who are using GC for various medical conditions.
Reviews, 1996
To systematically review the efficacy of etidronate on bone density, fractures and toxicity in po... more To systematically review the efficacy of etidronate on bone density, fractures and toxicity in postmenopausal women. We searched MEDLINE from 1966 to December 1998, examined citations of relevant articles, and the proceedings of international osteoporosis meetings. We contacted osteoporosis investigators to identify additional studies, primary authors, and pharmaceutical industry sources for unpublished data. We included thirteen trials (with 1010 participants) that randomized women to etidronate or an alternative (placebo or calcium and/or vitamin D) and measured bone density for at least one year. For each trial, three independent reviewers assessed the methodological quality and abstracted data. The data suggested a reduction in vertebral fractures with a pooled relative risk of 0.60% (95% CI 0.41 to 0.88). There was no effect on non-vertebral fractures (pooled relative risk 1.00, (95% CI 0.68 to 1.42)). Etidronate, relative to control, increased bone density after three years of treatment in the lumbar spine by 4.27% (95% CI 2.66 to 5.88), in the femoral neck by 2.19% (95% CI 0.43, 3.95) and in the total body by 0.97% (95% CI 0.39, 1.55). Effects were larger at 4 years, though the number of patients followed was much smaller. Etidronate increases bone density in the lumbar spine and femoral neck. The pooled estimates of fracture reduction with etidronate are consistent with a reduction in vertebral fractures, but no effect on non-vertebral fractures.
Reviews, 1996
ABSTRACT Corticosteroid-induced osteoporosis is a cause of morbidity in patients with chronic obs... more ABSTRACT Corticosteroid-induced osteoporosis is a cause of morbidity in patients with chronic obstructive lung disease, asthma, and rheumatologic disorders. Corticosteroid treatment causes bone loss by a variety of complex mechanisms. It has been shown that bone mineral loss at the hip averages 14% in the first year after starting corticosteroid therapy. To review the efficacy of calcitonin (subcutaneous or nasal) for the treatment and prevention of corticosteroid-induced osteoporosis. We conducted a search of Medline, the Cochrane Controlled Trials Register and Embase using the Cochrane Musculoskeletal Group search strategy for randomized controlled trials (RCTs) up to May 1998. We also searched bibliographic references and consulted content experts. Two independent reviewers selected RCTs which met predetermined inclusion criteria. Two reviewers independently extracted data using predetermined forms and assessed methodological quality of randomization, blinding and dropouts. For dichotomous outcomes, relative risks (RR) were calculated. For continuous data, weighted mean differences (WMD) of the percent change from baseline were calculated. We decided a priori to use random effects models for all outcomes, because of uncertainty about whether a consistent true effect exists in such different populations. Nine trials met the inclusion criteria, including 221 patients randomized to calcitonin and 220 to placebo. The median methodologic quality was two out of a maximum of five points. Calcitonin was more effective than placebo at preserving bone mass at the lumbar spine after six and 12 months of therapy with a WMD of 2.8% (95% CI: 1.4 to 4.3) and 3.2% (95% CI: 0.3 to 6.1). At 24 months, lumbar spine BMD was not statistically different between groups: WMD 4.5% (95% CI: -0.6 to 9.5)]. Bone density at the distal radius was also higher with calcitonin after six months of therapy, but bone density at the femoral neck was not different between placebo and calcitonin treated groups. The relative risk of fractures was not significantly different between calcitonin and placebo with a relative risk (RR) of 0.71 (95% CI: 0.26 to 1.89) for vertebral and 0.52 (95% CI: 0.14 to 1.96) for nonvertebral fractures. The subgroup analyses of methodological quality and duration of corticosteroid therapy were confounded. Trials of patients who had been taking steroids for greater than three months (which were of low methodologic quality) demonstrated a larger effect of calcitonin on spine bone density (about 6%) than prevention trials (about 1%). There was no consistent effect of different dosages (50-100 IU compared to 200-400 IU). However, subcutaneous calcitonin showed substantially greater prevention of bone loss. Withdrawals due to side effects were higher in the calcitonin-treated groups: RR 3.19 (95%CI: 0.66 to 15.47). Important side effects included nausea and facial flushing. Calcitonin appears to preserve bone mass in the first year of glucocorticoid therapy at the lumbar spine by about 3% compared to placebo, but not at the femoral neck. Our analysis suggests that the protective effect on bone mass may be greater for the treatment of patients who have been taking corticosteroids for more than three months. Efficacy of calcitonin for fracture prevention in steroid-induced osteoporosis remains to be established.
Journal of Aging Research, 2015
Objectives. To determine (1) whether intramuscular adipose tissue (IntraMAT) differs between wome... more Objectives. To determine (1) whether intramuscular adipose tissue (IntraMAT) differs between women with and without type 2 diabetes and (2) the association between IntraMAT and mobility and strength. Methods. 59 women ≥ 65 years with and without type 2 diabetes were included. A 1-Tesla MRI was used to acquire images of the leg. Timed-up-and-go (TUG) and grip strength were measured. Regression was used to determine associations between the following: (1) type 2 diabetes and IntraMAT (covariates: age, ethnicity, BMI, waist : hip ratio, and energy expenditure), (2) IntraMAT and TUG (covariates: diabetes, age, BMI, and energy expenditure), and IntraMAT and grip strength (covariates: diabetes, age, height, and lean mass). Results. Women with diabetes had more IntraMAT. After adjustment, IntraMAT was similar between groups (diabetes mean [SD] = 13.2 [1.4]%, controls 11.8 [1.3]%, = 0.515). IntraMAT was related to TUG and grip strength, but the relationships became nonsignificant after adjustment for covariates (difference/percent IntraMAT [95% CI]: TUG = 0.041 seconds [−0.079-0.161], = 0.498, grip strength = −0.144 kg [−0.335-0.066], = 0.175). Conclusions. IntraMAT alone may not be a clinically important predictor of functional mobility and strength; however, whether losses in functional mobility and strength are promoted by IntraMAT accumulation should be explored.
Background: Bisphosphonates are indicated in the prevention and treatment of osteoporosis. Howeve... more 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.
Journal of Clinical Densitometry, 2014
Part II of this 3-part series demonstrated 1-yr precision, standard error of the estimate, and 1-... more Part II of this 3-part series demonstrated 1-yr precision, standard error of the estimate, and 1-yr least significant change for volumetric bone outcomes determined using peripheral (p) quantitative computed tomography (QCT) and peripheral magnetic resonance imaging (pMRI) modalities in vivo. However, no clinically relevant outcomes have been linked to these measures of change. This study examined 97 women with mean age of 75 AE 9 yr and body mass index of 26.84 AE 4.77 kg/m 2 , demonstrating a lack of association between fragility fractures and standard deviation, least significant change and standard error of the estimate-based unit differences in volumetric bone outcomes derived from both pMRI and pQCT. Only cortical volumetric bone mineral density and cortical thickness derived from high-resolution pQCT images were associated with an increased odds for fractures. The same measures obtained by pQCT erred toward significance. Despite the smaller 1-yr and short-term precision error for measures at the tibia vs the radius, the associations with fractures observed at the radius were larger than at the tibia for highresolution pQCT. Unit differences in cortical thickness and cortical volumetric bone mineral density able to yield a 50% increase in odds for fractures were quantified here and suggested as a reference for future power computations.
Population Health Management, 2009
Family physicians&amp... more Family physicians' personal and practice characteristics may influence how osteoporosis is managed. Thus, we evaluated the impact of family physicians' personal and practice characteristics on the appropriate use of bone mineral density testing and osteoporosis therapy. The physician questionnaire assessed 13 personal and practice characteristics of the physicians. The patient questionnaire was used to collect data to ascertain how family physicians managed osteoporosis. A total of 225 family physicians from 7 provinces across Canada completed both the physician and patient questionnaires. The family physicians evaluated a total of 5601 patients. The generalized estimating equations technique was utilized to model the associations between family physicians' personal and practice characteristics and appropriate use of bone mineral density testing and osteoporosis therapy. Odds ratios (OR) and corresponding 95% confidence intervals (CI) are reported. Findings indicated that female family physicians have higher odds of administering appropriate bone density testing compared to male family physicians (OR: 1.28; 95% CI: 1.05, 1.55), and that physicians who have hospital privileges (OR: 0.77; 95% CI: 0.62, 0.97) and who graduated more recently from medical school (OR: 0.87; 95% CI: 0.77, 0.99) have lower odds of administering appropriate bone mineral density tests. Physicians who use electronic health records have higher odds of administering appropriate therapy (OR: 1.30; 95% CI: 1.06, 1.59) as compared to physicians who do not use them. Several family physicians' personal and practice characteristics are associated with appropriate utilization of bone mineral density testing and therapy. The education of both clinicians and policy makers regarding these new insights may translate to enhanced individual practices and an improved overall health care system to optimize the environment for managing osteoporosis.
Journal of the American Medical Directors Association, 2014
To evaluate the feasibility of implementing an interdisciplinary, multifaceted knowledge translat... more To evaluate the feasibility of implementing an interdisciplinary, multifaceted knowledge translation intervention within long-term care (LTC) and to identify any challenges that should be considered in designing future studies. Cluster randomized controlled trial. Forty LTC homes across the province of Ontario, Canada. LTC teams composed of physicians, nurses, pharmacists, and other staff. Cluster-level feasibility measures, including recruitment, retention, data completion, and participation in the intervention. A process evaluation was completed by directors of care indicating which process/policy changes had been implemented. Recruitment and retention rates were 22% and 63%, respectively. Good fidelity with the intervention was achieved, including attendance at educational meetings. After ViDOS, 7 process indicators were being newly implemented by more than 50% of active intervention homes. Despite recruitment and retention challenges, the multifaceted intervention produced a number of policy/process changes and had good intervention fidelity. This study is registered at ClinicalTrials.gov NCT01398527.
BMC Musculoskeletal Disorders, 2014
Background: To investigate the association between frailty index (FI) of deficit accumulation and... more 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 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.
SpringerPlus, 2013
Objective: Compare in vitro and in vivo characteristics and clinical outcomes of brand and generi... more Objective: Compare in vitro and in vivo characteristics and clinical outcomes of brand and generic alendronate. Research design and methods: Relevant search terms were input into Medline ("alendronate" AND "generic" up to August 5, 2013) and any abstracts deemed possibly relevant selected for full paper review and abstraction.
Canadian family physician Médecin de famille canadien, 2014
To outline the efficacy and risks of bisphosphonate therapy for the management of osteoporosis an... more 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." 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). 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 con...
The Osteoporosis Primer, 2000
The Journal of Clinical Endocrinology & Metabolism, 2014
Odanacatib (ODN), a selective cathepsin-K inhibitor, was found to increase bone mineral density (... more Odanacatib (ODN), a selective cathepsin-K inhibitor, was found to increase bone mineral density (BMD); the effect on fractures is based on adverse event reports. To estimate current effects and predict future effects of ODN on BMD and fractures. Electronic databases (Medline, EMBASE, Cochrane Library), conference proceedings, and bibliographies. Trials that compared ODN 50 mg/wk to placebo for at least 1 year and reported changes in BMD or fractures. Meta-analysis: Two bone outcomes were pooled as independent and as joint outcomes in Bayesian univariate and bivariate random-effects models. Of 32 potentially eligible articles, six citations describing four trials (993 patients) were included. ODN for 3 years increased mean BMD at the lumbar spine by 5.0% (95% credible interval [CrI], 2.7, 7.5), total hip by 3.6% (95% CrI, 1.6, 5.9), and femoral neck (FN) by 3.6% (95% CrI, 1.6, 5.7). In a future trial of 3-year duration, the predicted mean increase in BMD, adjusted for the effect on fractures, was 4.9% for lumbar spine (95% CrI, 2.5, 7.4), 3.4% for total hip (95% CrI, 1.7, 5.2), and 3.5% for FN (95% CrI, 1.8, 5.3). After accounting for the effect on FN BMD, ODN for 3 years was associated with a population odds ratio of 0.38 (95% CrI, 0.1, 0.8). In a future trial, the odds ratio was 0.41 (95% CrI, 0.1, 1.1). The probability of benefit on fractures was 96-99%. The estimates remained robust in sensitivity analyses. Our analyses suggest that ODN will increase BMD and decrease all fractures in the fracture outcome trial; however, direct demonstration of this antifracture efficacy is needed.
BoneKEy Reports, 2013
Our purpose was to identify factors for a parsimonious fracture risk assessment model considering... more Our purpose was to identify factors for a parsimonious fracture risk assessment model considering morphometric spine fracture status, femoral neck bone mineral density (BMD) and the World Health Organization (WHO) clinical risk factors. Using data from 2761 subjects from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective, longitudinal cohort study of randomly selected community-dwelling men and women aged X50 years, we previously reported that a logistic regression model considering age, BMD and spine fracture status provided as much predictive information as a model considering these factors plus the remaining WHO clinical risk factors. The current analysis assesses morphometric vertebral fracture and/or nonvertebral fragility fracture at 5 years using data from an additional 1964 CaMos subjects who have now completed 5 years of follow-up (total N ¼ 4725). Vertebral fractures were identified from lateral spine radiographs assessed using quantititative morphometry at baseline and end point. Nonvertebral fragility fractures were determined by questionnaire and confirmed using radiographs or medical records; fragility fracture was defined as occurring with minimal or no trauma. In this analysis, a model including age, BMD and spine fracture status provided a gradient of risk per s.d. (GR/s.d.) of 1.88 and captured most of the predictive information of a model including morphometric spine fracture status, BMD and all WHO clinical risk factors (GR/s.d. 1.92). For comparison, this model provided more information than a model considering BMD and the WHO clinical risk factors (GR/s.d. 1.74). These findings confirm the value of age, BMD and spine fracture status for predicting fracture risk.
Transplantation, 2001
Osteoporosis is a well-documented complication of organ transplantation. Bisphosphonates have bee... more Osteoporosis is a well-documented complication of organ transplantation. Bisphosphonates have been shown to be effective in preventing corticosteroid-induced osteoporosis in renal transplant recipients, but data are lacking for treatment of established osteoporosis. This study reports our clinical experience of treatment with the bisphosphonate etidronate in a single renal transplant center. To establish the effectiveness of etidronate in treating established low bone mineral density (BMD), all newly transplanted patients treated with etidronate were compared with controls. Twenty-five patients treated with etidronate (14 males, 11 females) and 24 controls (15 males, 9 females) were identified from the cohort of patients who underwent transplantation between January 1, 1994, and December 31, 1996. There was no difference in mean age, weight, or cumulative dose of corticosteroids between the treatment and control groups. The baseline BMD measurement was performed at 10.4 +/- 5.3 months after transplantation for treated patients and at 10.7 +/- 4.5 months for controls (P=0.78). Over the subsequent 1-year study period, patients treated with etidronate demonstrated a greater increase in BMD at sites with a preponderance of trabecular bone. Lumbar spine BMD increased 4.3 +/- 6.1% in the treatment group versus 0.55 +/ -5.3% in controls (P<0.03) and trochanter BMD increased 10.3 +/- 11.9% and 2.2 +/- 5.7%, respectively, in the treatment and control groups (P<0.02). This study establishes the effectiveness of etidronate for treatment of low BMD in renal transplant recipients. Patients selected for treatment had lower baseline BMD than control subjects, yet still showed a clinically important increase in BMD.
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Papers by Jonathan Adachi