More than 2.5 million women in the UK are at risk for fractures caused by weakened bones (osteoporosis) and may benefit from treatment to prevent these fractures from occurring. The goal of this study is to provide patients and their doctors with information about how often various harmful or unpleasant events happen among patients who use treatments for osteoporosis. We will select female patients in the CPRD GOLD and CPRD Aurum databases, aged 40 and older, who have used treatments for osteoporosis or who have prescriptions for vitamin D for bone health. We will describe how often patients using each type of drug have harmful or unpleasant events including heart attacks, strokes, sudden kidney failure, cancers, gastrointestinal discomfort/nausea, allergic reactions, and infections. We will also assess whether CPRD data and linked hospital information can be used to describe how often these patients have atypical femoral fractures or osteonecrosis of the jaw which are rare but serious conditions. We will describe how often each harmful or unpleasant event occurs by the type of drug the patient is using as well as by age, calendar year, severity of bone loss, and use or non-use of other drugs (corticosteroids and hormone replacement therapy) which can also affect bone health. Future studies will be able to use these results to help guide further research into whether certain osteoporosis drugs cause any of these unpleasant or harmful outcomes.
More than 2.5 million women in the UK are at risk for osteoporotic fractures and may benefit from treatment to prevent these fractures from occurring. The objective of this cohort study is to describe the safety and tolerability of treatments for the prevention of osteoporotic fracture among women in the UK. We will select all females aged 40 and older, who are new users of bisphosphonates, denosumab, teriparatide, raloxifene, tibolone or calcitonin in the years 2000 through 2020 in CPRD GOLD and CPRD Aurum. We will also select female users of vitamin D aged 40 or older with codes for osteoporosis/osteopenia/monitoring. We will then assess the feasibility of capturing cases of atypical femoral fractures and osteonecrosis of the jaw using information in the primary care and linked hospital records (HES APC). Additional outcomes will include major cardiovascular events, acute renal toxicities, osteosarcoma, esophageal cancer, liver cancer, gastrointestinal irritation, hypersensitivities, hyper/hypocalcemia, and infections. Using Byar’s method, we will estimate incidence rates, for each outcome, for each study drug, past use of any osteoporosis treatment or vitamin D only. Using Poisson regression, we will estimate incidence rate ratios for each outcome by study drug compared to the comparator group. For acute outcomes the comparator group will include both vitamin D only users and past users of osteoporosis treatments while for outcomes with delayed effects, such as cancer, the comparator will include vitamin D users only. Incidence rates and incidence rate ratios will be stratified by data source (GOLD vs Aurum), age, calendar time, disease severity, and concomitant use of corticosteroids and/or hormone replacement therapy. The results of this study will provide valuable data to clinicians to help inform patients choosing between treatment options. They will also provide important information for future studies related to the safety and tolerability of treatments for osteoporosis.
Safety outcomes: Atypical femoral fractures (AFF); osteonecrosis of the jaw (ONJ); any osteonecrosis; stroke; myocardial infarction; atrial fibrillation; venous thromboembolism; superficial thrombophlebitis; osteosarcoma; esophageal cancer; liver cancer; acute renal toxicity; allergic/hypersensitivity reactions; skin reactions; hypercalcemia; hypocalcemia; severe musculoskeletal pain; opportunistic infection; any infection
Tolerability outcomes: gastrointestinal irritation (nausea/vomiting); Acute flu-like reactions (aches, pain, fever); hormonal symptoms (hot flashes, leg cramps, vaginal discharge/postmenopausal bleeding)
Susan Jick - Chief Investigator - BCDSP - Boston Collaborative Drug Surveillance Program
Rebecca Persson - Corresponding Applicant - BCDSP - Boston Collaborative Drug Surveillance Program
Catherine Vasilakis-Scaramozza - Collaborator - BCDSP - Boston Collaborative Drug Surveillance Program
Katrina Hagberg - Collaborator - BCDSP - Boston Collaborative Drug Surveillance Program
Zarena Jafry - Collaborator - BCDSP - Boston Collaborative Drug Surveillance Program
HES Admitted Patient Care