This work provides a systematic review of the literature from January 2003 to April 2014 pertaining to the incidence, pathophysiology, diagnosis, and treatment of osteonecrosis of the jaw (ONJ), and offers recommendations for its management based on multidisciplinary international consensus. ONJ is associated with oncology-dose parenteral antiresorptive therapy of bisphosphonates (BP) and denosumab (Dmab). The incidence of ONJ is greatest in the oncology patient population (1% to 15%), where high doses of these medications are used at frequent intervals. In the osteoporosis patient population, the incidence of ONJ is estimated at 0.001% to 0.01%, marginally higher than the incidence in the general population (<0.001%). New insights into the pathophysiology of ONJ include antiresorptive effects of BPs and Dmab, effects of BPs on gamma delta T-cells and on monocyte and macrophage function, as well as the role of local bacterial infection, inflammation, and necrosis. Advances in imaging include the use of cone beam computerized tomography assessing cortical and cancellous architecture with lower radiation exposure, magnetic resonance imaging, bone scanning, and positron emission tomography, although plain films often suffice. Other risk factors for ONJ include glucocorticoid use, maxillary or mandibular bone surgery, poor oral hygiene, chronic inflammation, diabetes mellitus, illfitting dentures, as well as other drugs, including antiangiogenic agents. Prevention strategies for ONJ include elimination or stabilization of oral disease prior to initiation of antiresorptive agents, as well as maintenance of good oral hygiene. In those patients at high risk for the development of ONJ, including cancer patients receiving high-dose BP or Dmab therapy, consideration should be given to withholding antiresorptive therapy following extensive oral surgery until the surgical site heals with mature mucosal coverage. Management of ONJ is based on the stage of the disease, size of the lesions, and the presence of contributing drug therapy and comorbidity. Conservative therapy includes topical antibiotic oral rinses and systemic antibiotic therapy. Localized surgical debridement is indicated in advanced nonresponsive disease and has been successful. Early data have suggested enhanced osseous wound healing with teriparatide in those without contraindications for its use. Experimental therapy includes bone marrow stem cell intralesional transplantation, low-level laser therapy, local platelet-derived growth factor application, hyperbaric oxygen, and tissue grafting.

Since the publication of the Osteoporosis Canada guidelines in 2002, there has been a paradigm shift in the prevention and treatment of osteoporosis and fractures.1,2 The focus now is on preventing fragility fractures and their negative consequences, rather than on treating low bone mineral density, which is viewed as only one of several risk factors for fracture. Given that certain clinical factors increase the risk of fracture independent of bone mineral density, it is important to take an integrated approach and to base treatment decisions on the absolute risk of fracture. Current data suggest that many patients with fractures do not undergo appropriate assessment or treatment.3 To address this care gap for high-risk patients, the 2010 guidelines concentrate on the assessment and management of women and men over age 50 who are at high risk of fragility fractures and the integration of new tools for assessing the 10-year risk of fracture into overall management. Burden and care gapsFragility fractures, the consequence of osteoporosis, are responsible for excess mortality, morbidity, chronic pain, admission to institutions and economic costs. [4][5][6] They represent 80% of all fractures in menopausal women over age 50.3 Those with hip or vertebral fractures have substantially increased risk of death after the fracture.5 Postfracture mortality and institutionalization rates are higher for men than for women. 7Despite the high prevalence of fragility fractures in the Canadian population and the knowledge that fractures predict future fractures, 8 fewer than 20% of women 3,9 and 10% of men 10 receive therapies to prevent further fractures. These statistics contrast sharply with the situation for cardiovascular disease, where 75% of patients who have had myocardial infarction receive β-blockers to prevent another event. 11 Scope of the guidelinesThe target population for these guidelines is women and men over age 50, because of the overall burden of illness in that age group. As a consequence, we focused our systematic literature reviews on this population. The application of these guidelines to children and young adults, as well as high-risk groups such as transplant recipients, was considered, but indepth reviews of conditions that increase risk were largely beyond the scope of these guidelines. Development of the guidelinesThe development of these guidelines followed the Appraisal of Guidelines, Research and Evaluation (AGREE) framework. 12 We surveyed primary care physicians, patients, osteoporosis specialists from various disciplines, radiologists, allied health professionals and health policy-makers to identify priorities for these guidelines. We then conducted system-

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Context Hip fractures are a public health concern because they are associated with significant morbidity, excess mortality, and the majority of the costs directly attributable to osteoporosis. Objective To examine trends in hip fracture rates in Canada. Design, Setting, and Patients Ecologic trend study using nationwide hospitalization data for 1985 to 2005 from a database at the Canadian Institute for Health Information. Data for all patients with a hospitalization for which the primary reason was a hip fracture (570 872 hospitalizations) were analyzed. Main Outcome Measures Age-specific and age-standardized hip fracture rates. Results There was a decrease in age-specific hip fracture rates (all P for trend Ͻ.001). Over the 21-year period of the study, age-adjusted hip fracture rates decreased by 31.8% in females (from 118.6 to 80.9 fractures per 100 000 person-years) and by 25.0% in males (from 68.2 to 51.1 fractures per 100 000 person-years). Joinpoint regression analysis identified a change in the linear slope around 1996. For the overall population, the average age-adjusted annual percentage decrease in hip fracture rates was 1.2% (95% confidence interval, 1.0%-1.3%) per year from 1985 to 1996 and 2.4% (95% confidence interval, 2.1%-2.6%) per year from 1996 to 2005 (PϽ.001 for difference in slopes). Similar changes were seen in both females and males with greater slope reductions after 1996 (PϽ.001 for difference in slopes for each sex). Conclusions Age-standardized rates of hip fracture have steadily declined in Canada since 1985 and more rapidly during the later study period. The factors primarily responsible for the earlier reduction in hip fractures are unknown.

Fractures at typical osteoporotic sites are associated with increased mortality across all age groups, particularly in men. Better understanding of factors associated with increased post-fracture mortality should inform the development of management strategies.

BackgroundPopulation-based administrative data have been used to study osteoporosis-related fracture risk factors and outcomes, but there has been limited research about the validity of these data for ascertaining fracture cases. The objectives of this study were to: (a) compare fracture incidence estimates from administrative data with estimates from population-based clinically-validated data, and (b) test for differences in incidence estimates from multiple administrative data case definitions.MethodsThirty-five case definitions for incident fractures of the hip, wrist, humerus, and clinical vertebrae were constructed using diagnosis codes in hospital data and diagnosis and service codes in physician billing data from Manitoba, Canada. Clinically-validated fractures were identified from the Canadian Multicentre Osteoporosis Study (CaMos). Generalized linear models were used to test for differences in incidence estimates.ResultsFor hip fracture, sex-specific differences were observed in the magnitude of under- and over-ascertainment of administrative data case definitions when compared with CaMos data. The length of the fracture-free period to ascertain incident cases had a variable effect on over-ascertainment across fracture sites, as did the use of imaging, fixation, or repair service codes. Case definitions based on hospital data resulted in under-ascertainment of incident clinical vertebral fractures. There were no significant differences in trend estimates for wrist, humerus, and clinical vertebral case definitions.ConclusionsThe validity of administrative data for estimating fracture incidence depends on the site and features of the case definition.

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m 2 . In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, the...