Treatment of osteogenesis imperfecta with parathyroid hormone and zoledronic acid

INTERVENTION: Participants are randomised to one of two groups using minimisation to balance the groups for the following prognostic variables: 1. Clinical fracture during the two years prior to randomisation 2. Clinical subtype of OI (type I or others) 3. Gender 4. Lowest BMD T score at spine or hip (or Z‐score aged 18‐21) =‐2.5; or >‐2.5. 5. Age (=50; >50) 6. Bisphosphonate at entry or within 2 years prior to randomisation Intervention group: Participants will receive a 2‐year course of teriparatide 20mcg daily by subcutaneous injection. At the end of this period, participants will be given a single intravenous infusion of zoledronic acid 5mg. Control group: Participants will receive standard care, which may involve no bone specific treatment or treatment with bisphosphonates, depending on what the specialist that is normally responsible for treating participants’ osteogenesis imperfecta feels is most appropriate. This is an event driven study which will go on until 149 clinical fractures have occurred. Based on published data, this is expected to have occurred after an average of 48 months after the patient has enrolled into the study. Participants are reviewed at 12 months, 24 months and again at the end of study (this will on average be 48 months but it may vary between 36 and 60 months since the design is an event drive trial with a variable duration of follow up). At each visit the patient will get bloods checked and complete questionnaires. At baseline and 24 months a DEXA will be done. At baseline and 48 months (or study end) a spine‐x‐ray will be done. CONDITION: Osteogenesis imperfecta ; Musculoskeletal Diseases ; Osteogenesis Imperfecta PRIMARY OUTCOME: Proportion of participants experiencing a clinical fracture validated by x‐ray or other imaging at the final study visit (between 36‐60 months). SECONDARY OUTCOME: 1. Total number of clinical fractures experienced by participants validated by x‐ray or other imaging at the final study visit (between 36‐60 months); 2. Number of incident vertebral fractures assessed by imaging of the thoracic and lumbar spine at the final study visit (between 36‐60 months); 3. Total number of fractures experienced by participants defined as the combination validated clinical fractures and vertebral fractures and fractures reported by participants, where imaging was not performed, not feasible or where the results were inconclusive at the final study visit (between 36‐60 months); 4. Bone pain is assessed by the brief pain inventory (BPI) at 12 months, 24 months and at the end of study visit (between 36‐60 months); 5. Quality of life is assessed by the SF36 questionnaire at at 12 months, 24 months and at the end of study visit (between 36‐60 months); 6. Functional status is assessed by the health assessment questionnaire (HAQ) and EuroQol5D (EQ5D) assessment tools at at 12 months, 24 months and at the end of study visit(between 36‐60 months); 7. Adverse events reported by participants at 12 months, 24 months and at the end of study visit (between 36‐60 months) INCLUSION CRITERIA: 1. Adult patients age 18 years and over with a clinical diagnosis of osteogenesis imperfecta 2. Patients willing and able to consent and comply with the study protocol