Safety and tolerability of osteoporosis treatments in women

Date of Approval
Application Number
Technical Summary

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.

Health Outcomes to be Measured

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