Osteoporosis and Fracture Risk Reduction comep oct 2010

Notas do Editor

1. Asymptomatic versus asymptomatic
2. Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly Pivotal Fracture Trial Results of the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT) were published in the May 3, 2007, issue of The New England Journal of Medicine. Reference Black DM, Delmas PD, Eastell R, et al, for the HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356:1809-1822.
3. Study Population Postmenopausal women 65 to 89 years of age were eligible for inclusion if they had either a femoral neck T-score ≤–2.5 with or without evidence of an existing vertebral fracture or a femoral neck T-score ≤–1.5 with radiological evidence of at least 2 mild or 1 moderate vertebral fracture. Patients were excluded from the trial if they failed to meet a prespecified washout schedule for prior bisphosphonate use: Oral bisphosphonate for 48 weeks or more: 2 years Oral bisphosphonate for between 8 and 48 weeks: 1 year Oral bisphosphonate for between 2 and 8 weeks: 6 months Oral bisphosphonate for ≤2 weeks: 2 months Any IV bisphosphonate: 2 years Creatinine clearance was assessed at Visit 1 and Visit 2. Patients were excluded if they had a creatinine clearance of less than 30 mL/min or urine dipstick >2+ protein without evidence of contamination or bacteriuria on either visit. Patients with serum calcium >2.75 mmol/L or <2.0 mml/L were ineligible. Concomitant use of the following medications was allowed at baseline and during follow-up: hormone therapy (HT/ET), selective estrogen receptor modulators (SERMs) (eg, raloxifene, tamoxifen), calcitonin, tibolone, dehydroepiandrosterones, ipriflavone, and medroxyprogesterone. Patients were assigned to 1 of 2 treatment strata based on their current or planned osteoporosis treatment: Stratum I: no current osteoporosis medication and met washout criteria for prior medication (HT/ET, SERMs, calcitonin, tibolone) Use for 26 weeks or more: 1 year Use for 12 or more weeks, but less than 26 weeks: 6 months Use for 4 or more weeks, but less than 12 weeks: 3 months Use for less than 4 weeks: 1 month Stratum II: concomitant HT/ET, SERMs, calcitonin, or tibolone All patients were instructed to take calcium and vitamin D throughout the study Reference Black DM, Delmas PD, Eastell R, et al, for the HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356:1809-1822.
4. Zoledronic Acid Reduced Cumulative 3-Year Risk of Clinical Fractures (Hip, Clinical Vertebral, Non-vertebral) Zoledronic acid 5 mg consistently reduced the relative risk for fractures in key locations over 3 years : The rate of new hip fractures was 2.49% for placebo and 1.44% for ZOL 5 mg, corresponding to a significant 41% relative risk reduction with active drug (P =.0024) The event rate for clinical vertebral fractures was 2.59% in the placebo group, compared with 0.53% in the ZOL 5-mg group, corresponding to a significant 77% relative risk reduction with active drug (P < .001) The placebo group exhibited a non-vertebral fracture event rate of 10.71% versus 7.97% with ZOL 5 mg, for a significant 25% relative risk reduction (P =.0002). It should be noted that hip fracture was NOT excluded from analysis of non-vertebral fractures. Reference Black DM, Delmas PD, Eastell R, et al, for the HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356:1809-1822.
5. Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly Pivotal Fracture Trial Results of the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT) were published in the May 3, 2007, issue of The New England Journal of Medicine. Reference Black DM, Delmas PD, Eastell R, et al, for the HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356:1809-1822.
6. Zoledronic Acid Reduced Cumulative 3-Year Risk of Hip Fractures (Strata I + II) by 41% Over 3 years, ZOL 5 mg reduced the relative risk of incurring a hip fracture by 41%, compared with placebo (P < .001; hazard ratio = 0.59). Reference Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid 5 mg for treatment of postmenopausal osteoporosis. Submitted for publication. [citation to be updated when publication date is known]
7. Zoledronic Acid Reduced Cumulative 3-Year Risk of Hip Fractures (Strata I + II) by 41% Over 3 years, ZOL 5 mg reduced the relative risk of incurring a hip fracture by 41%, compared with placebo (P < .001; hazard ratio = 0.59). Reference Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid 5 mg for treatment of postmenopausal osteoporosis. Submitted for publication. [citation to be updated when publication date is known]
8. Table 1. Baseline Characteristics of the Subjects.
9. Table 2. Effect of Denosumab on the Risk of Fracture at 36 Months.
10. Figure 2. Percent Changes in Bone Mineral Density and Biochemical Markers of Bone Turnover. Changes in mean bone mineral density (BMD) at the lumbar spine (Panel A) and total hip (Panel B) are shown for 441 subjects who were included in a substudy of measurements of bone mineral density. As compared with subjects in the placebo group, subjects in the denosumab group had a relative increase of 9.2% in bone mineral density at the lumbar spine and 6.0% at the total hip. Changes in mean values for serum C-telopeptide of type I collagen (CTX) (Panel C) and serum procollagen type I N-terminal propeptide (PINP) (Panel D) are shown for 160 subjects who were included in a substudy of bone-turnover markers. P<0.001 for all between-group comparisons at all time points on the basis of analysis-of-covariance (ANCOVA) models. For bone mineral density, the comparisons were adjusted for study group, baseline bone mineral density, type of machine used to analyze bone mineral density, and interaction between the type of machine and the baseline bone mineral density; for CTX and PINP, the comparisons were calculated with the use of the Wilcoxon rank-sum test.
11. Figure 1. Incidence of New Vertebral, Nonvertebral, and Hip Fractures. The primary end point was the incidence of new vertebral fractures at 36 months (Panel A, left), which is shown for each study year (Panel A, right). Risk ratios (RRs) are for subjects in the group receiving denosumab, as compared with those receiving placebo. Kaplan-Meier curves of the time to the first nonvertebral fracture (Panel B) and the first hip fracture (Panel C) were determined on the basis of subjects who did not have a fracture or who did not leave the study before the time point of interest. The subjects at risk at 36 months included all those who completed end-of-study visits at or after the start of the window for the 36-month visit.
12. Table 3. Adverse Events.
13. Options of various countries under Asia, Europe, North America, Latin America and Oceania. Secondary osteoporosis classed as secondary to Insulin dependent DM, osteogenesis imperfecta in adults, chronic hyperthyroidism, hypoonadism, premature menopause (<45 years), chronic malnutrition, malabsorption, chronic liver disease. Can be calculated on base of BMI if BMD not known. There are paper versions available for males/females, 10 year prob of hip#/major #, based on BMI/BMD for a selection of countries
14. Falls risk not included as there is not pharmacological intervention to address falls risk
15. 3 diagnostic criteria for BONJ: 1. current or previous use f BP 2. exposed, necrotic bone in maxillofacial region for ≥8/52 3. no hx of XRT to jaws ~60% some pain at initial presentation, but many asymptomatic