Osteoporosis: Josse RG

Khan AA, Sándor GK, Dore E, Morrison AD, Alsahli M, Amin F, Peters E, Hanley DA, Chaudry SR, Dempster DW, Glorieux FH, Neville AJ, Talwar RM, Clokie CM, Al Mardini M, Paul T, Khosla S, Josse RG, Sutherland S, Lam DK, Carmichael RP, Blanas N, Kendler D, Petak S, St-Marie LG, Brown J, Evans AW, Rios L, Compston JE, Anonymous00076. · Divisions of Endocrinology and Geriatrics, McMaster University, Hamilton, Ontario, Canada. · J Rheumatol. · Pubmed #18528958 No free full text.

Abstract: OBJECTIVE: Following publication of the first reports of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates in 2003, a call for national multidisciplinary guidelines based upon a systematic review of the current evidence was made by the Canadian Association of Oral and Maxillofacial Surgeons (CAOMS) in association with national and international societies concerned with ONJ. The purpose of the guidelines is to provide recommendations regarding diagnosis, identification of at-risk patients, and prevention and management strategies, based on current evidence and consensus. These guidelines were developed for medical and dental practitioners as well as for oral pathologists and related specialists. METHODS: The multidisciplinary task force established by the CAOMS reviewed all relevant areas of research relating to ONJ associated with bisphosphonate use and completed a systematic review of current literature. These evidence-based guidelines were developed utilizing a structured development methodology. A modified Delphi consensus process enabled consensus among the multidisciplinary task force members. These guidelines have since been reviewed by external experts and endorsed by national and international medical, dental, oral surgery, and oral pathology societies. RESULTS: Recommendations regarding diagnosis, prevention, and management of ONJ were made following analysis of all current data pertaining to this condition. ONJ has many etiologic factors including head and neck irradiation, trauma, periodontal disease, local malignancy, chemotherapy, and glucocorticoid therapy. High-dose intravenous bisphosphonates have been identified as a risk factor for ONJ in the oncology patient population. Low-dose bisphosphonate use in patients with osteoporosis or other metabolic bone disease has not been causally linked to the development of ONJ. Prevention, staging, and treatment recommendations are based upon collective expert opinion and current data, which has been limited to case reports, case series, surveys, retrospective studies, and 2 prospective observational studies. Recommendations: In all oncology patients, a thorough dental examination including radiographs should be completed prior to the initiation of intravenous bisphosphonate therapy. In this population, any invasive dental procedure is ideally completed prior to the initiation of high-dose bisphosphonate therapy. Non-urgent procedures are preferably delayed for 3 to 6 months following interruption of bisphosphonate therapy. Osteoporosis patients receiving oral or intravenous bisphosphonates do not require a dental examination prior to initiating therapy in the presence of appropriate dental care and good oral hygiene. Stopping smoking, limiting alcohol intake, and maintaining good oral hygiene should be emphasized for all patients receiving bisphosphonate therapy. Individuals with established ONJ are most appropriately managed with supportive care including pain control, treatment of secondary infection, removal of necrotic debris, and mobile sequestrate. Aggressive debridement is contraindicated. CONCLUSION: Our multidisciplinary guidelines, which provide a rational evidence-based approach to the diagnosis, prevention, and management of bisphosphonate-associated ONJ in Canada, are based on the best available published data and the opinion of national and international experts involved in the prevention and management of ONJ.

Lentle BC, Brown JP, Khan A, Leslie WD, Levesque J, Lyons DJ, Siminoski K, Tarulli G, Josse RG, Hodsman A, Anonymous00004, Anonymous00005. · Department of Radiology, University of British Columbia, Vancouver, BC. · Can Assoc Radiol J. · Pubmed #17408160 No free full text.

Abstract: OBJECTIVE: Given the increasing evidence that vertebral fractures are underdiagnosed and not acted on, Osteoporosis Canada and the Canadian Association of Radiologists initiated a project to develop and publish a set of recommendations to promote and facilitate the diagnosis and reporting of vertebral fractures. OPTIONS: The identification of spinal fractures is not uniform. More than 65% of vertebral fractures cause no symptoms. It is also apparent that vertebral fractures are inadequately recognized when the opportunity for diagnosis arises fortuitously. It is to patients' benefit that radiologists report vertebral fractures evident on a chest or other radiograph, no matter how incidental to the immediate clinical indication for the examination. OUTCOMES: The present recommendations can help to close the gap in care in recognizing and treating vertebral fractures, to prevent future fractures and thus reduce the burden of osteoporosis-related morbidity and mortality, as well as fracture-related costs to the health care system. EVIDENCE: Several studies indicate that a gap exists in regard to the diagnosis of vertebral fractures and the clinical response following such diagnosis. All recommendations presented here are based on consensus. VALUES: These recommendations were developed by a multidisciplinary working group under the auspices of the Scientific Advisory Council of Osteoporosis Canada and the Canadian Association of Radiologists. BENEFITS, HARM, AND COSTS: Prevalent vertebral fractures have important clinical implications in terms of future fracture risk. Recognizing and reporting fractures incidental to radiologic examinations done for other reasons has the potential to reduce health care costs by initiating further steps in osteoporosis diagnosis and appropriate therapy. RECOMMENDATIONS: Physicians should be aware of the importance of vertebral fracture diagnosis in assessing future osteoporotic fracture risk. Vertebral fractures incidental to radiologic examinations done for other reasons should be identified and reported. Vertebral fractures should be assessed from lateral spinal or chest radiographs according to the semiquantitative method of Genant and colleagues. Grade II and Grade III fractures as classified by this method should be given the greatest emphasis. Semiquantitative fracture recognition should include the recognition of changes such as loss of vertebral end-plate parallelism, cortical interruptions, and quantitative changes in the anterior, midbody, and posterior heights of vertebral bodies. When spine radiographs are performed to assess the presence of vertebral fractures, anteroposterior examinations may assist in the initial evaluation. The standard follow-up need only consist of single lateral views of the thoracic and lumbar spine that include T4 to L4 vertebrae. The radiographic technique described in this paper, or a technique of comparable efficacy, should be used. Dual X-ray absorptiometry examinations that include lateral spinal morphological assessments (vertebral fracture assessment) may contribute to fracture recognition. Educational material about the clinical importance of vertebral fracture recognition as a potential indicator of future osteoporotic fracture risk with its associated morbidity and mortality should be directed to all physicians. VALIDATION: Recommendations were based on consensus opinion.

Khan AA, Hanley DA, Bilezikian JP, Binkley N, Brown JP, Hodsman AB, Josse RG, Kendler DL, Lewiecki EM, Miller PD, Olszynski WP, Petak SM, Syed ZA, Theriault D, Watts NB, Anonymous00369. · Division of Endocrinology, McMaster University, Hamilton, Ontario, Canada, and Hanover General Hospital, PA, USA. · J Clin Densitom. · Pubmed #16731431 No free full text.

Abstract: This document addresses skeletal health assessment in individuals with secondary causes of osteoporosis. Recommendations are based on consensus of the Canadian Panel of the International Society for Clinical Densitometry and invited international experts. Bone mineral density (BMD) testing in these populations is performed in conjunction with careful evaluation of the disease state contributing to bone loss and increased fragility fracture risk, as well as assessment of other contributing risk factors for fracture. The presence of secondary causes of bone loss may further increase the risk of fracture independently of BMD and may necessitate earlier pharmacologic intervention. Dual-energy X-ray absorptiometry is indicated in the initial workup of secondary causes of osteoporosis. The BMD fracture risk relationship is not known for individuals with chronic renal failure (CRF). The BMD testing in this population may be normal in the presence of skeletal fragility, and quantitative bone histomorphometry is better at evaluating skeletal status than BMD in CRF. Dual-energy X-ray absorptiometry is a valuable tool in assessing skeletal health in individuals with secondary causes of osteoporosis.

Siminoski K, Leslie WD, Frame H, Hodsman A, Josse RG, Khan A, Lentle BC, Lévesque J, Lyons DJ, Tarulli G, Brown JP, Anonymous00424. · Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, AB. · Can Assoc Radiol J. · Pubmed #16144280 No free full text.

Abstract: OBJECTIVE: To propose a set of recommendations for optimal bone mineral density (BMD) reporting in postmenopausal women and older men and to provide clinicians with both a BMD diagnostic category and a useful tool to assess an individual's risk of osteoporotic fracture. OPTIONS: The current methods of BMD reporting were reviewed. In this document, we propose that an individual's 10-year absolute fracture risk, rather than BMD alone, be used for fracture risk categorization. Consequently, age, sex, BMD, fragility fracture history, and glucocorticoid use are the basis for the approach outlined in this document. OUTCOMES: An optimal BMD report as proposed in this document will provide clinicians with both a BMD diagnostic category and a useful tool to assess an individual's risk of osteoporotic fracture. A BMD report format, a checklist, and a patient questionnaire are meant to further encourage its use. EVIDENCE: All recommendations were developed using a consensus from clinicians and experts in the field of BMD testing and a standard method for the evaluation and citation of the supporting evidence. VALUES: These recommendations were developed by a multidisciplinary working group under the auspices of the Scientific Advisory Council of the Osteoporosis Society of Canada and the Canadian Association of Radiologists. BENEFITS, HARM, AND COSTS: Optimal BMD reports help the practitioner to assess an individual's risk for osteoporotic fracture and to decide whether medical therapy is warranted. RECOMMENDATIONS: The BMD report should include: patient identifiers. Dual-energy X-ray absorptiometry (DXA) scanner identifier. BMD results expressed in absolute values (g/cm2; 3 decimal places) and T-score (1 decimal place) for lumbar spine; proximal femur (total hip, femoral neck, and trochanter); and an alternate site (forearm BMD preferred: 1/3 radius, 33% radius or proximal radius) if either hip or spine is not valid. A statement about any limitations due to artifacts, if present. The fracture risk category (low, moderate, or high) as determined by using Tables 3 and 4 and by including major clinical factors that modify absolute fracture risk probability (with an indication of the corresponding absolute 10-year fracture risk of <10%, 10-20%, or >20%). A statement as to whether the change is statistically significant or not for serial measurements. The BMD centre's least significant change for each skeletal site (in g/cm2) should be included. VALIDATION: Recommendations were based on consensus opinion. Since these are the first Canadian recommendations integrating clinical risk factors in a quantitative fracture risk assessment, it is anticipated that these "Recommendations for BMD Reporting in Canada" will be a work in progress and will be updated periodically to accommodate advances in this field.

Khan AA, Bachrach L, Brown JP, Hanley DA, Josse RG, Kendler DL, Leib ES, Lentle BC, Leslie WD, Lewiecki EM, Miller PD, Nicholson RL, O'Brien C, Olszynski WP, Theriault MY, Watts NB, Anonymous00235. · Divisions of Endocrinology and Geriatrics, McMaster University, Hamilton, ON, Canada. · J Clin Densitom. · Pubmed #14742888 No free full text.

Abstract: 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.

Khan AA, Sándor GK, Dore E, Morrison AD, Alsahli M, Amin F, Peters E, Hanley DA, Chaudry SR, Lentle B, Dempster DW, Glorieux FH, Neville AJ, Talwar RM, Clokie CM, Mardini MA, Paul T, Khosla S, Josse RG, Sutherland S, Lam DK, Carmichael RP, Blanas N, Kendler D, Petak S, Ste-Marie LG, Brown J, Evans AW, Rios L, Compston JE, Anonymous00115. · Divisions of Endocrinology and Geriatrics, McMaster University, Oakville, ON L6J 1X8, Canada. · J Rheumatol. · Pubmed #19286860 No free full text.

Abstract: In 2003, the first reports describing osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BP) were published. These cases occurred in patients with cancer receiving high-dose intravenous BP; however, 5% of the cases were in patients with osteoporosis receiving low-dose bisphosphonate therapy. We present the results of a systematic review of the incidence, risk factors, diagnosis, prevention, and treatment of BP associated ONJ. We conducted a comprehensive literature search for relevant studies on BP associated ONJ in oncology and osteoporosis patients published before February 2008.All selected relevant articles were sorted by area of focus. Data for each area were abstracted by 2 independent reviewers. The results showed that the diagnosis is made clinically. Prospective data evaluating the incidence and etiologic factors are very limited. In oncology patients receiving high-dose intravenous BP, ONJ appears to be dependent on the dose and duration of therapy, with an estimated incidence of 1%-12% at 36 months of exposure. In osteoporosis patients, it is rare, with an estimated incidence < 1 case per 100,000 person-years of exposure. The incidence of ONJ in the general population is not known. Currently, there is insufficient evidence to confirm a causal link between low-dose BP use in the osteoporosis patient population and ONJ. We concluded BP associated ONJ is associated with high-dose BP therapy primarily in the oncology patient population. Prevention and treatment strategies are currently based on expert opinion and focus on maintaining good oral hygiene and conservative surgical intervention.

Saad F, Adachi JD, Brown JP, Canning LA, Gelmon KA, Josse RG, Pritchard KI. · Department of Surgery/Urology, Centre Hospitalier de l'Université de Montréal, University of Montreal, Montreal, Quebec, Canada. · J Clin Oncol. · Pubmed #18955443 No free full text.

Abstract: PURPOSE: Bone loss resulting from the treatment of breast and prostate cancer is an emerging problem. Bisphosphonates have a potential role in the prevention of this cancer treatment-induced bone loss (CTIBL). METHODS: Studies evaluating the incidence and prevalence of CTIBL in early breast and prostate cancer patients and trials evaluating the preventative role of bisphosphonates were identified by a search of the PubMed and Cochrane Library databases through the end of March 2008. Reference lists from retrieved articles were cross referenced, and further information was obtained from relevant scientific meetings. RESULTS: Several therapies commonly used in the treatment of women and men with breast and prostate cancers, in particular the aromatase inhibitors (AIs) for breast cancer and androgen deprivation therapy (ADT) for prostate cancer, are associated with significant bone loss and with an increase in fracture risk. The use of bisphosphonates seems to attenuate the bone loss, although the long-term impact remains unclear because of insufficient follow-up. CONCLUSION: Adjuvant endocrine therapy with an AI or androgen deprivation can be considered a risk factor for the development of osteopenia, osteoporosis, and bone fracture, which can be mitigated by appropriate bisphosphonate therapy. Clear identification of risk factors for osteoporosis in individual patients should aid treatment decisions about whether to use bisphosphonates when starting or switching to an AI or ADT. Patients need to be educated about this risk and other measures to avoid this complication, including lifestyle modifications that may benefit their general and bone health.

Khan AA, Colquhoun A, Hanley DA, Jankowski LG, Josse RG, Kendler DL, Lentle B, Leslie WD, Lewiecki EM, O'neill E, Robertson S, Syed ZA, Tanner SB, Webster D. · Division of Endocrinology, McMaster University, Hamilton, Ontario, Canada. · J Clin Densitom. · Pubmed #17485038 No free full text.

This publication has no abstract.

Siminoski K, Leslie WD, Frame H, Hodsman A, Josse RG, Khan A, Lentle BC, Levesque J, Lyons DJ, Tarulli G, Brown JP. · Department of Radiology and Diagnostic Imaging and Division of Endocrinology and Metabolism, Department of Medicine, University of Alberta, Edmonton, Canada. · J Clin Densitom. · Pubmed #17485028 No free full text.

Abstract: In June 2005, new Canadian recommendations for bone mineral density (BMD) reporting in postmenopausal women and older men were published by Osteoporosis Canada (formerly the Osteoporosis Society of Canada) and the Canadian Association of Radiologists. The recommendations were developed by a multidisciplinary working group that included the Canadian Panel of the International Society for Clinical Densitometry and were reviewed and endorsed by multiple stakeholders. Previous Canadian osteoporosis guidelines advised intervention based on an individual's World Health Organization category (normal, osteopenia, or osteoporosis) as a marker of relative fracture risk. In the new approach, an individual's 10-yr absolute fracture risk, rather than BMD alone, is used for fracture risk categorization. Absolute fracture risk is determined using not only BMD results, but also age, sex, fragility fracture history, and glucocorticoid use. A procedure is presented for estimating absolute 10-yr fracture risk in untreated individuals, leading to assigning an individual to 1 of 3 absolute fracture risk categories: low risk (<10% 10-yr fracture risk), moderate risk (10-20%), and high risk (>20%). We propose that an individual's absolute fracture risk category should be the basis for deciding on treatment and frequency of BMD monitoring.

Brown JP, Josse RG, Anonymous00114. · Division of Rheumatology, Centre de recherche du CHUL, Université Laval, Canada. · CMAJ. · Pubmed #12427685 links to  free full text

Abstract: OBJECTIVE: To revise and expand the 1996 Osteoporosis Society of Canada clinical practice guidelines for the management of osteoporosis, incorporating recent advances in diagnosis, prevention and management of osteoporosis, and to identify and assess the evidence supporting the recommendations. OPTIONS: All aspects of osteoporosis care and its fracture complications - including classification, diagnosis, management and methods for screening, as well as prevention and reducing fracture risk - were reviewed, revised as required and expressed as a set of recommendations. OUTCOMES: Strategies for identifying and evaluating those at high risk; the use of bone mineral density and biochemical markers in diagnosis and assessing response to management; recommendations regarding nutrition and physical activity; and the selection of pharmacologic therapy for the prevention and management of osteoporosis in men and women and for osteoporosis resulting from glucocorticoid treatment. EVIDENCE: All recommendations were developed using a justifiable and reproducible process involving an explicit method for the evaluation and citation of supporting evidence. VALUES: All recommendations were reviewed by members of the Scientific Advisory Council of the Osteoporosis Society of Canada, an expert steering committee and others, including family physicians, dietitians, therapists and representatives of various medical specialties involved in osteoporosis care (geriatric medicine, rheumatology, endocrinology, obstetrics and gynecology, nephrology, radiology) as well as methodologists from across Canada. Benefits, harm and costs: Earlier diagnosis and prevention of fractures should decrease the medical, social and economic burdens of this disease. RECOMMENDATIONS: This document outlines detailed recommendations pertaining to all aspects of osteoporosis. Strategies for identifying those at increased risk (i.e., those with at least one major or 2 minor risk factors) and screening with central dual-energy x-ray absorptiometry at age 65 years are recommended. Bisphosphonates and raloxifene are first-line therapies in the prevention and treatment of postmenopausal osteoporosis. Estrogen and progestin/progesterone is a first-line therapy in the prevention and a second-line therapy in the treatment of postmenopausal osteoporosis. Nasal calcitonin is a second-line therapy in the treatment of postmenopausal osteoporosis. Although not yet approved for use in Canada, hPTH(1-34) is expected to be a first-line treatment for postmenopausal women with severe osteoporosis. Ipriflavone, vitamin K and fluoride are not recommended. Bisphosphonates are the first-line therapy for the prevention and treatment of osteoporosis in patients requiring prolonged glucocorticoid therapy and for men with osteoporosis. Nasal or parenteral calcitonin is a first-line treatment for pain associated with acute vertebral fractures. Impact-type exercise and age-appropriate calcium and vitamin D intake are recommended for the prevention of osteoporosis. VALIDATION: All recommendations were graded according to the strength of the evidence; where the evidence was insufficient and recommendations were based on consensus opinion alone, this is indicated. These guidelines are viewed as a work in progress and will be updated periodically in response to advances in this field.

Adachi JD, Olszynski WP, Hanley DA, Hodsman AB, Kendler DL, Siminoski KG, Brown J, Cowden EA, Goltzman D, Ioannidis G, Josse RG, Ste-Marie LG, Tenenhouse AM, Davison KS, Blocka KL, Pollock AP, Sibley J. · Department of Medicine, St Joseph's Hospital, McMaster University, Hamilton, Ontario, Canada. · Semin Arthritis Rheum. · Pubmed #10707991 No free full text.

Abstract: OBJECTIVES: To educate scientists and health care providers about the effects of corticosteroids on bone, and advise clinicians of the appropriate treatments for patients receiving corticosteroids. METHODS: This review summarizes the pathophysiology of corticosteroid-induced osteoporosis, describes the assessment methods used to evaluate this condition, examines the results of clinical trials of drugs, and explores a practical approach to the management of corticosteroid-induced osteoporosis based on data collected from published articles. RESULTS: Despite our lack of understanding about the biological mechanisms leading to corticosteroid-induced bone loss, effective therapy has been developed. Bisphosphonate therapy is beneficial in both the prevention and treatment of corticosteroid-induced osteoporosis. The data for the bisphosphonates are more compelling than for any other agent. For patients who have been treated but continue to lose bone, hormone replacement therapy, calcitonin, fluoride, or anabolic hormones should be considered. Calcium should be used only as an adjunctive therapy in the treatment or prevention of corticosteroid-induced bone loss and should be administered in combination with other agents. Conclusions: Bisphosphonates have shown significant treatment benefit and are the agents of choice for both the treatment and prevention of corticosteroid-induced osteoporosis.

Watts NB, Josse RG, Hamdy RC, Hughes RA, Manhart MD, Barton I, Calligeros D, Felsenberg D. · University of Cincinnati, Cincinnati, Ohio 45219, USA. · J Clin Endocrinol Metab. · Pubmed #12574177 links to  free full text

Abstract: Independent risk factors for fracture include advanced age, preexisting fractures, and low bone mineral density. Rised-ronate has been shown in several large trials to be safe and effective for patients with osteoporosis, but its effects in populations at high risk are not well characterized. To determine the effect of risedronate on vertebral fracture in high-risk subjects, we pooled data from two randomized, double-blind studies [Vertebral Efficacy with Risedronate Therapy (VERT) Multinational (VERT-MN) and VERT-North America (VERT-NA)] in 3684 postmenopausal osteoporotic women treated with placebo or risedronate 2.5 or 5 mg/d and analyzed fracture risk in subgroups of subjects at high risk for fracture due to greater age or more prevalent fractures (vs. median for overall study population), or lower bone mineral density (T-score, -2.5 or less). Fractures were diagnosed by quantitative and semiquantitative assessment of radiographs at baseline and 1 yr. In the overall population, treatment for 1 yr with risedronate 5 mg/d reduced the risk of new vertebral fractures by 62% vs. control (relative risk, 0.38; 95% confidence interval, 0.25, 0.56; P < 0.001) and of multiple new vertebral fractures by 90% vs. control (relative risk, 0.10; 95% confidence interval, 0.04, 0.26; P < 0.001). Consistent risk reductions were observed at 1 yr in the risedronate-treated high-risk subgroups. Significant reduction in fracture risk after 1 yr is an important benefit in patients at high risk for fracture because, without treatment, these patients are likely to sustain new fractures in the near term.

Kendler DL, Adachi JD, Josse RG, Slosman DO. · University of British Columbia, Vancouver, BC, Canada. · Osteoporos Int. · Pubmed #19266136 No free full text.

Abstract: PURPOSE: The purpose of this study was to review the monitoring of strontium ranelate osteoporosis therapy. METHODS: The method used in this study was comprehensive literature review with clinical perspectives. RESULTS: Changes in bone turnover markers (BTM) or bone mineral density (BMD) have been documented in osteoporosis clinical trials. However, neither BMD nor BTM changes fully explain the observed fracture risk reduction in treated patients. If changes in BMD or BTM on therapy would be easily discernable in individual patients, and were strongly associated with fracture risk reduction, monitoring individuals would be more useful. BMD changes in patients on strontium ranelate are of a greater magnitude and hence can be easily determined in an individual patient. In addition, there exists a better correlation between fracture risk reduction and increases in BMD. CONCLUSIONS: The strong correlation between measured BMD increases and fracture risk reduction in patients on strontium ranelate therapy will be of clinical benefit to physicians wishing to evaluate both treatment persistence and fracture risk reduction.

Chen P, Krege JH, Adachi JD, Prior JC, Tenenhouse A, Brown JP, Papadimitropoulos E, Kreiger N, Olszynski WP, Josse RG, Goltzman D, Anonymous00060. · Eli Lilly and Company, Indianapolis, Indiana, USA. · J Bone Miner Res. · Pubmed #19016585 No free full text.

Abstract: Vertebral fractures are the most common osteoporotic fracture, and patients with prevalent vertebral fractures have a greater risk of future fractures. However, radiographically determined vertebral fractures are not identified as a distinct risk factor in the World Health Organization (WHO) fracture risk assessment tool. The objective of this study was to evaluate and compare potential risk factors including morphometric spine fracture status and the WHO risk factors for predicting 5-yr fracture risk. We hypothesized that spine fracture status provides prognostic information in addition to consideration of the WHO risk factors alone. A randomly selected, population-based community cohort of 2761 noninstitutionalized men and women > or =50 yr of age living within 50 km of one of nine regional centers was enrolled in the Canadian Multicentre Osteoporosis Study (CaMOS), a prospective and longitudinal cohort study following subjects for 5 yr. Prevalent and incident spine fractures were identified from lateral spine radiographs. Incident nonvertebral fragility fractures were determined by an annual, mailed fracture questionnaire with validation, and nonvertebral fragility fracture was defined by investigators as a fracture with minimal trauma. A model considering the WHO risk factors plus spine fracture status provided greater prognostic information regarding future fracture risk than a model considering the WHO risk factors alone. In univariate analyses, age, BMD, and spine fracture status had the highest gradient of risk. A model considering these three risk factors captured almost all of the predictive information provided by a model considering spine fracture status plus the WHO risk factors and provided greater predictive information than a model considering the WHO risk factors alone. The use of spine fracture status along with age and BMD predicted future fracture risk with greater simplicity and higher prognostic accuracy than consideration of the risk factors included in the WHO tool.

Berger C, Langsetmo L, Joseph L, Hanley DA, Davison KS, Josse RG, Prior JC, Kreiger N, Tenenhouse A, Goltzman D, Anonymous00201. · CaMos Methods Centre, McGill University, Montreal, Quebec, Canada. · J Bone Miner Res. · Pubmed #18847328 No free full text.

Abstract: Our objective was to estimate the relationship between longitudinal change in BMD and fragility fractures. We studied 3635 women and 1417 men 50-85 yr of age in the Canadian Multicentre Osteoporosis Study who had at least two BMD measurements (lumbar spine, femoral neck, total hip, and trochanter) within the first 5 yr of the study and fragility fractures (any, main, forearm/wrist, ribs, hip) within the first 7 yr. Multiple logistic regression was used to model the relationship between baseline BMD, BMD change, and fragility fractures. We found that, among nonusers of antiresorptives, independent of baseline BMD, a decrease of 0.01 g/cm(2)/yr in total hip BMD was associated with an increased risk of fragility fracture with ORs of 1.15 (95% CI: 1.01; 1.32) in women and 1.34 (95% CI: 1.02; 1.78) in men. The risk of fragility fractures in subgroups such as fast losers and those with osteopenia was better estimated by models that included BMD change than by models that included baseline BMD but excluded BMD change. Although the association between baseline BMD and fragility fractures was similar in users and nonusers of antiresorptives, the association was stronger in nonusers compared with users. These results show that BMD change in both men and women is an independent risk factor for fragility fractures and also predicts fracture risk in those with osteopenia. The results suggest that BMD change should be included with other variables in a comprehensive fracture prediction model to capture its contribution to osteoporotic fracture risk.

Papaioannou A, Kennedy CC, Ioannidis G, Sawka A, Hopman WM, Pickard L, Brown JP, Josse RG, Kaiser S, Anastassiades T, Goltzman D, Papadimitropoulos M, Tenenhouse A, Prior JC, Olszynski WP, Adachi JD, Anonymous00108. · McMaster University, Hamilton Health Sciences-Chedoke Site, Hamilton, ON, Canada. · Osteoporos Int. · Pubmed #18802659 No free full text.

Abstract: Using prospective data from the Canadian Multicentre Osteoporosis Study (CaMos), we compared health utilities index (HUI) scores after 5 years of follow-up among participants (50 years and older) with and without incident clinical fractures. Incident fractures had a negative impact on HUI scores over time. INTRODUCTION: This study examined change in health-related quality of life (HRQL) in those with and without incident clinical fractures as measured by the HUI. METHODS: The study cohort was 4,820 women and 1,783 men (50 years and older) from the CaMos. The HUI was administered at baseline and year 5. Participants were sub-divided into incident fracture groups (hip, rib, spine, forearm, pelvis, other) and were compared with those without these fractures. The effects of both time and fracture type on HUI scores were examined in multivariable regression analyses. RESULTS: Men and women with hip fractures, compared to those without, had lower HUI measures that ranged from -0.05 to -0.25. Both women and men with spine fractures had significant deficits on the pain attributes (-0.07 to -0.12). In women, self-care (-0.06), mobility and ambulation (-0.05) were also negatively impacted. Women with rib fractures had deficits similar to women with spine fractures, and these effects persisted over time. In men, rib fractures did not significantly affect HUI scores. Pelvic and forearm fractures did not substantially influence HUI scores. CONCLUSION: The HUI was a sensitive measure of HRQL change over time. These results will inform economic analyses evaluating osteoporosis therapies.

Jamal SA, Goltzman D, Hanley DA, Papaioannou A, Prior JC, Josse RG. · Medicine, University of Toronto, Toronto, ON, Canada. · Osteoporos Int. · Pubmed #18800179 No free full text.

Abstract: Nitrates may have beneficial effects on bone. To determine if nitrates were associated with increased bone mineral density (BMD), we conducted a secondary analysis using data from subjects in a prospective study. Subjects reporting nitrate use had increased BMD compared with non-users, confirming that nitrates have positive BMD effects in women and men. INTRODUCTION: Prior studies suggest positive associations between nitrates and bone. METHODS: We used linear regression models, stratified by gender and adjusted for age, weight, and baseline differences, to determine the association between daily nitrate use and BMD among subjects participating in the Canadian Multicentre Osteoporosis Study. All results are reported as annualised percent change in BMD at the hip and spine among nitrate users compared to non-users. RESULTS: We included 1,419 men (71 reported daily nitrate use) and 2,587 women (97 reported daily nitrate use). Male non-users had decreased hip BMD (-1.3%; 95% confidence interval [95%CI] = -1.6 to -1.1) and increased spine BMD (2.8%; 95%CI = 2.5 to 3.1). Male nitrate users had increased hip BMD (1.4%; 95%CI = 0.1 to 2.8) and spine BMD (4.5%; 95%CI = 3.2 to 5.7). Among women, non-users had decreased hip BMD (-1.9; 95%CI = -2.1 to -1.7) and increased spine BMD (2.1%; 95%CI = 1.9 to 2.4) whilst users had an increase in hip BMD (2.0%; 95%CI = 1.2 to 2.8) and spine BMD (4.1%; 95%CI = 3.4 to 4.9). CONCLUSION: Nitrate use is associated with increased BMD at the hip and spine in men and women.

Papaioannou A, Kennedy CC, Ioannidis G, Gao Y, Sawka AM, Goltzman D, Tenenhouse A, Pickard L, Olszynski WP, Davison KS, Kaiser S, Josse RG, Kreiger N, Hanley DA, Prior JC, Brown JP, Anastassiades T, Adachi JD, Anonymous00061. · Division of Geriatric Medicine, McMaster University, Hamilton Health Sciences-Chedoke Site, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada. · Osteoporos Int. · Pubmed #17924051 No free full text.

Abstract: SUMMARY: We examined osteoporosis diagnosis/treatment in 2,187 community dwelling men age 50+. After five years in the study, 90% of men with fragility fractures remained undiagnosed and untreated for osteoporosis. The need to treat fragility fractures is well established in guidelines, and these numbers represent an important care gap. INTRODUCTION: Whether physicians in the community are recognizing and appropriately treating osteoporosis and fragility fractures in men remains unknown. We examined the rate of diagnosis and treatment in community dwelling men participating in the Canadian Multicentre Osteoporosis Study (CaMos). METHODS: Between February 1996 and September 2002, 2,187 participants were recruited from nine sites across Canada and prospectively followed. Information on osteoporosis diagnosis, fractures, medications were collected annually by a detailed questionnaire. DXA examination of lumbar spine (L1-4) and hip were conducted at baseline and year five. RESULTS: Diagnosis and treatment in men with clinical fragility fractures was low: at baseline and year five only 2.3% and 10.3% of men with a clinical fracture reported an osteoporosis diagnosis, respectively. At year five, 90% of men with a clinical fragility fracture were untreated. Hip fractures were the most commonly treated (37.5% by year five). A diagnosis of osteoporosis resulted in greater treatment: 67% of participants with diagnosed osteoporosis were treated with a bisphosphonate and 87% were taking calcium and/or vitamin D (year five). CONCLUSIONS: In this population-based study, both a diagnostic and therapeutic gap existed between knowledge and practice related to fragility fractures and osteoporosis in men aged >or=50 years.

Cranney A, Jamal SA, Tsang JF, Josse RG, Leslie WD. · Clinical Epidemiology Program, Ottawa Health Research Institute, Ottawa, Ont. · CMAJ. · Pubmed #17846439 links to  free full text

Abstract: BACKGROUND: The study objectives were to determine fracture rates in relation to bone mineral density at various central skeletal sites, using the World Health Organization definition for osteoporosis (T-score -2.5 or less), and to contrast fracture patterns among women 50 to 64 years of age with those among women 65 years of age and older. METHODS: Historical cohort study with a mean observation period of 3.2 (standard deviation [SD] 1.5) years. The study group (16,505 women 50 years of age or older) was drawn from the Manitoba Bone Density Program database, which includes all bone mineral density results for Manitoba. Baseline density measurements for the lumbar spine and hip were performed with dual-energy x-ray absorptiometry. Outcomes included the percentage of osteoporotic fractures and the rates of fracture and excess fracture (per 1000 person-years) among postmenopausal women with osteopenia and osteoporosis relative to those with normal bone mineral density (according to the classification of the World Health Organization). RESULTS: The mean age was 65 (SD 9) years, and the mean T-scores for all sites fell within the osteopenic category. There were 765 incident fractures (fracture rate 14.5 [95% confidence interval, CI, 13.5-15.6 [per 1000 person-years). Fracture rates were significantly higher among women 65 years of age or older than among women 50-64 years of age (21.6 [95% CI 19.7-23.4] v. 8.6 [95% CI 7.5-9.7] per 1000 person-years, p < 0.001). Although fracture rates were significantly higher among women with osteoporotic T-scores, most fractures occurred in women with nonosteoporotic values (min-max: 59.7%-67.8%). INTERPRETATION: In this study, most of the postmenopausal women with osteoporotic fractures had nonosteoporotic bone mineral density values. This finding highlights the importance of considering key clinical risk factors that operate independently of bone mineral density (such as age) when assessing fracture risk.

Chong CA, Diaz-Granados N, Hawker GA, Jamal S, Josse RG, Cheung AM. · Division of General Internal Medicine and Clinical Epidemiology, University Health Network and Mount Sinai Hospital, University of Toronto, Toronto, Canada. · Osteoporos Int. · Pubmed #17603742 No free full text.

Abstract: SUMMARY: We describe complementary and alternative medicine use (CAM) in 360 patients attending osteoporosis clinics. Of these patients, 57% were CAM users. Predictors of CAM use included lower mental quality of life, younger age and higher education. Less than half of CAM use was disclosed to physicians, despite potential adverse interactions. INTRODUCTION: The prevalence of complementary and alternative medicine (CAM) use in osteoporosis clinics is not known. The objective of this study was to describe the pattern of CAM use in this population. METHODS: We performed a cross-sectional study of 360 patients attending academic osteoporosis clinics in Toronto, Canada in 2001. Subjects completed a self-administered questionnaire on CAM use. Health-related quality of life (HQL) was measured with the Short-Form 36v2. Comparative statistics and logistic regression were performed to identify sociodemographic, HQL and clinical correlates of CAM use. RESULTS: More than 80% of participants were women, Caucasian and had at least a high school education. Of subjects, 57% used CAM in the previous year. Only 44% of CAM use was disclosed to a medical doctor. CAM users and non-users did not differ in clinical characteristics such as bone mineral density, level of comorbidity and fracture history. In univariate analysis, CAM users were less satisfied with conventional medicine. However, when we explored patient satisfaction, comorbidities and sociodemographic as predictors for CAM use, the multivariable analyses showed that lower mental HQL, younger age, and post-secondary education were the only significant predictors. We identified 35 cases in which the utilization of CAM supplements could possibly exacerbate existing medical conditions. CONCLUSION: Patients attending osteoporosis clinics frequently use CAM. Conceptually, the predictors of use identified in this study may fit into a socio-behavioral model that helps explain why people turn to CAM. Physicians may need to elicit a history of CAM use more vigilantly so as to better screen for possible adverse clinical interactions.

Richards JB, Leslie WD, Joseph L, Siminoski K, Hanley DA, Adachi JD, Brown JP, Morin S, Papaioannou A, Josse RG, Prior JC, Davison KS, Tenenhouse A, Goltzman D, Anonymous00336. · Department of Medicine, McGill University, Montreal, Quebec, Canada. · J Bone Miner Res. · Pubmed #17129177 No free full text.

Abstract: The impact of clinical risk factor-based absolute risk methods on the prevalence of high risk for osteoporotic fracture is unknown. We applied absolute risk methods to 6646 subjects and found that the prevalence of elderly women deemed to be at high risk increased substantially, whereas the overall prevalence was highly dependent on the threshold used to designate high risk. INTRODUCTION: Many groups have advocated using absolute risk methods that incorporate clinical risk factors to target patients for osteoporosis therapy. We examined how the application of such absolute risk classification systems influences the prevalence of those considered to be at high risk for osteoporotic fracture and compared these systems to one based solely on BMD. MATERIALS AND METHODS: Using 6646 subjects from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective, randomly selected, population-based cohort, we assessed three different systems for determining prevalence of high risk for osteoporotic fracture: a BMD-based system; a simplified risk factor system incorporating age, sex, BMD, and two clinical risk factors; and a comprehensive system, incorporating age, sex, BMD, and seven clinical risk factors. The 10-year absolute risks of incident fragility fracture were compared across systems using three different high-risk thresholds. RESULTS: The prevalence of a T score < or = -2.5 was 18.8% (95% CI: 17.7-19.9%) in women and 3.9% (95% CI: 3.0-4.7%) in men. Using a 15% 10-year risk of fracture threshold, the prevalence of women at high risk increased to 46.9% (95% CI: 45.4-48.4) and 42.5% (95% CI: 41.1-43.9) when the comprehensive and simplified risk factor classification systems were used, respectively. Using a 25% 10-year absolute risk threshold, the prevalence of high risk was similar to that of the BMD-based system, whereas the 20% threshold gave intermediate rates. All thresholds analyzed resulted in an increased prevalence of older women at high risk for fracture, whereas only the 15% 10-year risk of fracture threshold resulted in an increase in the prevalence of men at high risk. CONCLUSIONS: The application of risk factor-based systems results in an increased prevalence of older women at high risk. The prevalence of individuals at high risk may increase with changes to the methods used to determine those who are eligible for therapy. These data have important implications for the pattern of care and costs of treating osteoporotic fractures.

Sawka AM, Papaioannou A, Josse RG, Murray TM, Ioannidis G, Hanley DA, Prior JC, Thabane L, Papadimitropoulos EA, Gafni A, Pickard L, Anastassiades T, Kirkland S, Adachi JD, The CaMos Research Group. · Department of Medicine, Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada. · J Clin Densitom. · Pubmed #17097526 No free full text.

Abstract: Routine bone mineral densitometry (BMD) screening has been recommended for women aged >or=65 yr (Osteoporosis Canada [OC], International Society for Clinical Densitometry [ISCD], Canadian and United States Task Forces on Preventative Healthcare, and National Osteoporosis Foundation) and for men >or=65 yr (OC) or >or=70 yr (ISCD). We estimated the number of older Canadians needed to screen (NNS) by BMD to detect an undiagnosed case of osteoporosis, using prospective, multicenter, population-based data from the Canadian Multicentre Osteoporosis Study (CaMos). We included participants aged >or=65 yr with baseline dual-energy X-ray absorptiometry (DXA) BMDs at the femoral neck and lumbar spine (L1-L4). Osteoporosis was defined by a T-score <or=2.5 at either site. Patients were questioned about a prior diagnosis of osteoporosis. We studied 2699 women and 1032 men aged >or=65 yr. The percentage prevalence and 95% confidence intervals were determined. In individuals aged >or=65 yr, the prevalence of osteoporosis was 25.6% in women (95% confidence interval, 24.0%, 27.3%) and 8.9% in men (7.3%, 10.8%). In 652 men aged >or=70 yr, the prevalence of osteoporosis was 11.3% (9.1%, 14.0%). Of the participants with BMD-defined osteoporosis, 76.6% of woman aged >or=65 yr (73.2%, 79.6%; 516 of 674 women), 93.4% of men aged >or=65 yr (86.4%, 96.9%; 85 of 91), and 93.2% of men >or=70 yr (84.9%, 97.0%; 68 of 73) were not aware of it. Thus, the minimum NNS by BMD testing to detect one previously undiagnosed case of osteoporosis in Canada is: 6 women aged >or=65 yr, 13 men aged >or=65 yr, and 10 men aged >or=70 yr.

Rao LG, Mackinnon ES, Josse RG, Murray TM, Strauss A, Rao AV. · Division of Endocrinology and Metabolism, Department of Medicine, St. Michael's Hospital, Toronto, ON, Canada. · Osteoporos Int. · Pubmed #16941193 No free full text.

Abstract: INTRODUCTION: Oxidative stress induced by reactive oxygen species (ROS) is associated with the risk of osteoporosis, and can be reduced by certain dietary antioxidants. Lycopene is an antioxidant known to decrease the risk of age-related chronic diseases, such as cancer. However, the role of lycopene in osteoporosis has not yet been investigated. MATERIALS AND METHODS: In a cross-sectional study, 33 postmenopausal women aged 50-60 years provided seven-day dietary records and blood samples. Serum samples were used to measure serum lycopene, lipid peroxidation, protein thiols, bone alkaline phosphatase (BAP), and cross-linked N-telopeptides of type I collagen (NTx). The serum lycopene per kilogram body weight of the participants was grouped into quartiles and associated with the above serum parameters using one-way ANOVA and the Newman-Keuls post-test. RESULTS: The results showed that groups with higher lycopene intake, as determined from the dietary records, had higher serum lycopene (p<0.02). A higher serum lycopene was found to be associated with a low NTx (p<0.005). Similarly, groups with higher serum lycopene had lower protein oxidation (p<0.05). DISCUSSION: In conclusion, these results suggest that the dietary antioxidant lycopene reduces oxidative stress and the levels of bone turnover markers in postmenopausal women, and may be beneficial in reducing the risk of osteoporosis.

Perez EA, Josse RG, Pritchard KI, Ingle JN, Martino S, Findlay BP, Shenkier TN, Tozer RG, Palmer MJ, Shepherd LE, Liu S, Tu D, Goss PE. · St Michael's Hospital, Toronto, Canada. · J Clin Oncol. · Pubmed #16822845 No free full text.

Abstract: PURPOSE: Aromatase inhibition depletes estrogen levels and may be associated with accelerated bone resorption. The National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) study MA.17B evaluated bone turnover markers and bone mineral density (BMD) in postmenopausal women randomly assigned to MA.17, a placebo-controlled trial of letrozole after standard adjuvant tamoxifen. PATIENTS AND METHODS: Eligible women had a baseline BMD T score of at least 2.0 in either the hip or L2-4 spine; all received calcium 500 mg and vitamin D 400 U daily. Percentage change in BMD (L2-L4 spine and hip) at 12 and 24 months, rate of osteoporosis, and change in markers of bone formation (serum bone alkaline phosphatase) and resorption (serum C-telopeptide and urine N-telopeptide) at 6, 12, and 24 months were compared. RESULTS: Two hundred twenty-six patients (122 letrozole, 104 placebo) were enrolled. Baseline characteristics were similar in the two groups, including BMD, median age of 60.7 years (81% < 70 years), and median follow-up of 1.6 years. At 24 months, patients receiving letrozole had a significant decrease in total hip BMD (-3.6% v -0.71%; P = .044) and lumbar spine BMD (-5.35% v -0.70%; P = .008). Letrozole increased urine N-telopeptide at 6, 12, and 24 months (P = .054, < .001, and .016, respectively). No patient went below the threshold for osteoporosis in total hip BMD, whereas at the L2-L4 (posteroanterior view), more women became osteoporotic by BMD while receiving letrozole (4.1% v 0%; P = .064). CONCLUSION: After 5 years of adjuvant tamoxifen, subsequent letrozole causes a modest increase in bone resorption and reduction in bone mineral density in the spine and hip compared to placebo. Further follow-up is necessary to evaluate the long-term clinical implications of this difference.

Bogoch ER, Elliot-Gibson V, Beaton DE, Jamal SA, Josse RG, Murray TM. · St. Michael's Hospital, University of Toronto, 55 Queen Street East, Suite 800, Toronto, ON M5C 1R6, Canada. · J Bone Joint Surg Am. · Pubmed #16391246 No free full text.

Abstract: BACKGROUND: Fragility fractures resulting from osteoporosis are common injuries. However, the identification and treatment of osteoporosis in these high-risk patients are widely reported to be inadequate. The goals of this study were to determine how many patients receiving inpatient or outpatient treatment for a fragility fracture could be identified and enrolled in a program for osteoporosis education, investigation, and treatment and receive appropriate osteoporosis care within the program. METHODS: An Osteoporosis Exemplary Care Program was implemented to identify, educate, evaluate, refer, and treat patients considered to be at risk for osteoporosis because of a typical fragility fracture. System modifications included coordination among the orthopaedic unit, Metabolic Bone Disease Clinic, and nuclear medicine unit to provide a continuum of care for these patients. Barriers were addressed through ongoing education of physicians, staff, and patients to increase knowledge and awareness of osteoporosis. The percentages of patients previously diagnosed and treated for osteoporosis, referred for investigation of osteoporosis, treated by the orthopaedic team, and receiving appropriate attention for osteoporosis were calculated. Risk factors for osteoporosis were also assessed. RESULTS: Three hundred and forty-nine patients with a fragility fracture (221 outpatients and 128 inpatients) who met the inclusion criteria and an additional eighty-one patients with a fracture (fifty-five outpatients and twenty-six inpatients) who did not meet the inclusion criteria but were suspected by their orthopaedic surgeons of having underlying osteoporosis were enrolled in the Osteoporosis Exemplary Care Program. More than 96% (414) of these 430 patients received appropriate attention for osteoporosis. Approximately one-third (146) of the 430 patients had been diagnosed and treated for osteoporosis before the time of recruitment. Two hundred and twenty-two of the remaining patients were referred to the Metabolic Bone Disease Clinic or to their family physician for further investigation and treatment for osteoporosis. Treatment was initiated by the orthopaedic team for another twenty-three patients. Many patients had risk factors for osteoporosis in addition to the fragility fracture; these included a previous fracture (forty-nine of 187; 26%), a mother who had had a fragility fracture (forty-two of 188; 22%), or a history of smoking (105 of 188; 56%). CONCLUSIONS: In a coordinated post-fracture osteoporosis education and treatment program directed at patients with a fragility fracture and their caregivers, >95% of patients were appropriately diagnosed, treated, or referred for osteoporosis care. To accomplish this, a dedicated coordinator and the full cooperation of orthopaedic surgeons and residents, orthopaedic technologists, allied health-care professionals (nurses, physical and occupational therapists, and social workers), and administrative staff were required.