Oral glucocorticoids are potent anti-inflammatory and immunosuppressant agents used to treat and control several conditions. However, oral glucocorticoid exposure leads to an osteoporotic state characterized by increased bone loss and fracture risk. Bone loss is rapid upon oral glucocorticoid exposure, particularly in the vertebra. Osteoporosis treatment are often recommended for patients receiving oral glucocorticoids to prevent fracture. However, osteoporosis drug benefit in randomized controlled trials and observational studies is not yet established among oral glucocorticoid users. This research aimed to estimate fracture rates among new and ongoing oral glucocorticoid users and assess the benefit of osteoporosis drugs. First, meta-analytic methods were leveraged to pool fracture data from randomized clinical trials and examine fracture rates by oral glucocorticoid exposure history. Second, network meta-analysis was used to estimate the relative efficacy of osteoporosis drugs among oral glucocorticoid users. Third, using Ontario administrative healthcare data, three cohort analyses were conducted to assess the effectiveness of alendronate, etidronate, and risedronate in reducing fracture risk among chronic oral glucocorticoid users. Results of the meta-analytic analyses (study 1) showed that vertebral and non-vertebral fracture rates are higher among patients starting a new oral glucocorticoid treatment course than patients with ongoing use. These findings are consistent with higher bone loss among glucocorticoid initiators than ongoing users. The network meta-analysis (study 2) showed etidronate, risedronate, and teriparatide as efficacious in preventing vertebral fracture; teriparatide was identified as the most efficacious treatment followed by risedronate. No treatment was associated with a reduction in hip fracture risk, yet the data were limited to small pooled samples of heterogeneous patients in clinical trials. Results of the large population-based observational research (study 3) support the effectiveness of alendronate and risedronate to reduce hip fracture risk, and all three oral bisphosphonates to reduce vertebral fracture risk. The findings of this dissertation draw attention to the high fracture risk among new oral glucocorticoid users and provide evidence of the benefit of osteoporosis drugs early upon oral glucocorticoid exposure to reduce fracture risk. Further research is required to examine fracture risk by different glucocorticoid exposure patterns and estimate the comparative effectiveness between osteoporosis drugs.Ph.D
