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-

Vertebral compression is a serious complication of childhood acute lymphoblastic leukemia (ALL). The prevalence and pattern of vertebral fractures, as well as their relationship to BMD and other clinical indices, have not been systematically studied. We evaluated spine health in 186 newly diagnosed children (median age, 5.3 yr; 108 boys) with ALL (precursor B cell: N = 167; T cell: N = 19) who were enrolled in a national bone health research program. Patients were assessed within 30 days of diagnosis by lateral thoraco-lumbar spine radiograph, bone age (also used for metacarpal morphometry), and BMD. Vertebral morphometry was carried out by the Genant semiquantitative method. Twenty-nine patients (16%) had a total of 75 grade 1 or higher prevalent vertebral compression fractures (53 thoracic, 71%; 22 lumbar). Grade 1 fractures as the worst grade were present in 14 children (48%), 9 patients (31%) had grade 2 fractures, and 6 children (21%) had grade 3 fractures. The distribution of spine fracture was bimodal, with most occurring in the midthoracic and thoraco-lumbar regions. Children with grade 1 or higher vertebral compression had reduced lumbar spine (LS) areal BMD Z-scores compared with those without (mean ± SD, 22.1 ± 1.5 versus 21.1 ± 1.2; p < 0.001). LS BMD Z-score, second metacarpal percent cortical area Z-score, and back pain were associated with increased odds for fracture. For every 1 SD reduction in LS BMD Z-score, the odds for fracture increased by 80% (95% CI: 10-193%); the presence of back pain had an OR of 4.7 (95% CI: 1.5-14.5). These results show that vertebral compression is an under-recognized complication of newly diagnosed ALL. Whether the fractures will resolve through bone growth during or after leukemia chemotherapy remains to be determined.

Objective To evaluate the continued efficacy and safety of alendronate (ALN) for up to 2 years in patients receiving glucocorticoids. Methods This is a 12‐month extension of a previously completed 1‐year trial of daily ALN, performed to evaluate the effects of ALN over a total of 2 years in 66 men and 142 women continuing to receive at least 7.5 mg of prednisone or equivalent daily. All patients received supplemental calcium and vitamin D. The primary end point was the mean percentage change in lumbar spine bone mineral density (BMD) from baseline to 24 months. Other outcomes included changes in hip and total body BMD, biochemical markers of bone turnover, radiographic joint damage of the hands, and vertebral fracture incidence. Results The mean (±SEM) lumbar spine BMD increased by 2.8 ± 0.6%, 3.9 ± 0.7%, and 3.7 ± 0.6%, respectively, in the groups that received 5 mg, 10 mg, and 2.5/10 mg of ALN daily (P ≤ 0.001) and decreased by −0.8 ± 0.6% in the placebo group (P not significant) over 24 months. In patients receiving any dose of ALN, BMD was increased at the trochanter (P ≤ 0.05) and maintained at the femoral neck. Total body BMD was increased in patients receiving 5 or 10 mg ALN (P ≤ 0.01). These 2 dose levels of ALN were more effective than placebo at all sites (P ≤ 0.05). Bone turnover markers (N‐telopeptides of type I collagen and bone‐specific alkaline phosphatase) decreased 60% and 25%, respectively, during treatment with ALN (P ≤ 0.05). There were fewer patients with new vertebral fractures in the ALN group versus the placebo group (0.7% versus 6.8%; P = 0.026). The safety profile was similar between treatment groups. Conclusion Alendronate is an effective, well‐tolerated therapy for the prevention and treatment of glucocorticoid‐induced osteoporosis, with sustained treatment advantages for up to 2 years.

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This is the first study demonstrating persistent sarcopenia associated with poorer growth and recurrent hospitalization in children post-LTx.

Objective. Vertebral fractures are an under-recognized problem in children with inflammatory disorders. We studied spine health among 134 children (87 girls) with rheumatic conditions (median age 10 years) within 30 days of initiating glucocorticoid therapy. Methods. Children were categorized as follows: juvenile dermatomyositis (n ‫؍‬ 30), juvenile idiopathic arthritis (n ‫؍‬ 28), systemic lupus erythematosus and related conditions (n ‫؍‬ 26), systemic arthritis (n ‫؍‬ 22), systemic vasculitis (n ‫؍‬ 16), and other conditions (n ‫؍‬ 12). Thoracolumbar spine radiograph and dual x-ray absorptiometry for lumbar spine (L-spine) areal bone mineral density (BMD) were performed within 30 days of glucocorticoid initiation. Genant semiquantitative grading was used for vertebral morphometry. Second metacarpal morphometry was carried out on a hand radiograph. Clinical factors including disease and physical activity, calcium and vitamin D intake, cumulative glucocorticoid dose, underlying diagnosis, L-spine BMD Z score, and back pain were analyzed for association with vertebral fracture. Results. Thirteen vertebral fractures were noted in 9 children (7%). Of these, 6 patients had a single vertebral fracture and 3 had 2-3 fractures. Fractures were clustered in the mid-thoracic region (69%). Three vertebral fractures (23%) were moderate (grade 2); the others were mild (grade 1). For the entire cohort, mean ؎ SD L-spine BMD Z score was significantly different from zero (؊0.55 ؎ 1.2, P < 0.001) despite a mean height Z score that was similar to the healthy average (0.02 ؎ 1.0, P ‫؍‬ 0.825). Back pain was highly associated with increased odds for fracture (odds ratio 10.6 [95% confidence interval 2.1-53.8], P ‫؍‬ 0.004). Conclusion. In pediatric rheumatic conditions, vertebral fractures can be present prior to prolonged glucocorticoid exposure.

Purpose-Vertebral fractures due to osteoporosis are a potential complication of childhood acute lymphoblastic leukemia (ALL). To date, the incidence of vertebral fractures during ALL treatment has not been reported. CIHR Author ManuscriptCIHR Author Manuscript CIHR Author ManuscriptPatient and Methods-We prospectively evaluated 155 children with ALL during the first 12 months of leukemia therapy. Lateral thoracolumbar spine radiographs were obtained at baseline and 12 months. Vertebral bodies were assessed for incident vertebral fractures using the Genant semi-quantitative method, and relevant clinical indices such as spine bone mineral density (BMD), back pain and the presence of vertebral fractures at baseline were analyzed for association with incident vertebral fractures.Results-Of the 155 children, 25 (16%, 95% Confidence Interval (CI) 11% to 23%) had a total of 61 incident vertebral fractures, of which 32 (52%) were moderate or severe. Thirteen of the 25 children with incident vertebral fractures (52%) also had fractures at baseline. Vertebral fractures at baseline increased the odds of an incident fracture at 12 months by an odds ratio of 7.3 (95% CI 2.3 to 23.1, p = 0.001). In addition, for every one standard deviation reduction in spine BMD Zscore at baseline, there was 1.8-fold increased odds of incident vertebral fracture at 12 months (95% CI 1.2 to 2.7, p = 0.006).Conclusion-Children with ALL have a high incidence of vertebral fractures after 12 months of chemotherapy, and the presence of vertebral fractures and reductions in spine BMD Z-scores at baseline are highly associated clinical features.

Osteoporotic fractures are a significant cause of morbidity in acute lymphoblastic leukemia (ALL). Our objective was to determine the incidence and predictors of fractures and recovery from osteoporosis in pediatric ALL over 6 years following glucocorticoid initiation. Vertebral fractures (VF) and vertebral body reshaping were assessed on annual spine radiographs, low-trauma non-VF were recorded at regular intervals and spine bone mineral density (BMD) was captured every 6 months for 4 years and then annually. A total of 186 children with ALL were enrolled (median age 5.3 years; range, 1.3 to 17.0 years). The cumulative fracture incidence was 32.5% for VF and 23.0% for non-VF; 39.0% of children with VF were asymptomatic. No fractures occurred in the sixth year and 71.3% of incident fractures occurred in the first 2 years. Baseline VF, cumulative glucocorticoid dose, and baseline lumbar spine (LS) BMD Z-score predicted both VF and non-VF. Vertebral body reshaping following VF was incomplete or absent in 22.7% of children. Those with residual vertebral deformity following VF were older compared to those without (median age 8.0 years at baseline [interquartile range {IQR}, 5.5 to 9.4] versus 4.8 years [IQR, 3.6 to 6.2], p = 0.04) and had more severe vertebral collapse (median maximum spinal deformity index 3.5 [IQR, 1.0 to 8.0] versus 0.5 [IQR, 0.0 to 1.0], p = 0.01). VF and low LS BMD Z-score at baseline as well as glucocorticoid exposure predicted incident VF and non-VF. Nearly 25% of children had persistent vertebral deformity following VF, more frequent in older children, and in those with more severe collapse. These results suggest the need for trials addressing interventions in the first 2 years of chemotherapy, targeting older children and children with more severe vertebral collapse, because these children are at greatest risk for incident VF and subsequent residual vertebral deformity. © 2018 American Society for Bone and Mineral Research.