Approximately, a total of 2,669 patients (95%CI: 2,570–2,772) would be currently diagnosed with OI in Spain, which represents an estimated prevalence of 0.56:10,000 inhabitants. Among them, 715 (95%CI: 664–769) are children and 1,954 (95%CI: 1,869–2,043) are adults, representing a prevalence of 0.88 (95%CI: 0.81–0.94) and 0.50 (95%CI: 0.48–0.52) per 10,000 inhabitants, respectively. It was estimated that approximately 269 (95%CI: 238–303) new patients are diagnosed with OI every year in Spain which represents an estimated annual incidence of 0.06 (95%CI: 0.05–0.06) per 10,000 inhabitants per year. Approximately, 97 (95%CI: 79–118) would be paediatric and 172 (95%CI: 148–200) adult patients, which represents a paediatric incidence of 0.12 (95%CI: 0.10–0.14) and an adult incidence of 0.04 (95%CI: 0.04–0.05) per 10,000 inhabitants per year. The estimated prevalence and annual incidence of OI in Spain are presented in Table 1. 

Patients with OI are geographically disseminated, usually needing to travel to other healthcare areas or regions to be diagnosed and followed up. More than half of the patients with OI (53%) under the care of the clinicians participating in the study are referred from other healthcare areas (45%) or other regions (8%) to be diagnosed. Furthermore, 52% of patients are usually referred from other healthcare areas (38%) or from other regions (14%) for their regular follow up.

OI's skeletal and extra-skeletal characteristics and symptoms, including long bone deformities, scoliosis/kyphosis, low BMD, chronic pain, fatigue, and psychological disorders, are more common in adult patients than in paediatric patients, according to the data reported by the participants. Dentinogenesis imperfecta is more frequently diagnosed in paediatric patients because adults often have a worse dentin status naturally, leading to underdiagnosis in adult patients with OI. The median percentage of patients suffering from each skeletal and extra-skeletal characteristic and symptom derived from OI that reached agreement among experts (CV ≥1) are presented in Table 2, along with the interquartile range (IQR) reflecting the variability in the results inherent to the condition.

Despite the agreement that clinical features of OI can seriously impact the quality of life (QoL) of patients, most clinicians (89%) do not perform a QoL assessment on a regular basis mainly due to the lack of validated tools and available time in clinical practice.

Experts reported that approximately 22.5% (IQR 10.0%—30.0%) of OI patients suffer at least one fracture per year. Regarding the number of fractures per patient and year, OI patients experience a median of 1 (IQR 0.4–1.2) fracture per year. Considering the type of fractures, 20.0% (IQR 3.4%—29.5%) would be vertebral and 80% non-vertebral. Of these, 31.2% (IQR 10.0%—50.0%) can be classified as milder, 42.6% (IQR 30.0%—54.5%) as moderately severe and 26.3% (IQR 10.0%—40.0%) as severe. For the purposes of the Delphi study, non-vertebral mild, moderate, and severe fractures are defined as fractures not requiring patients visiting a healthcare centre, those requiring medical intervention in a healthcare centre and fractures that require surgical intervention, respectively. Table 3 shows the incidence of fractures in OI patients.

OI patients go through a median of 1 (IQR 0.1–1.0) hospitalisation per year, and fractures are the main cause of hospitalisation. In each in-patient period, they stay a median of 3 (IQR 2.0–5.0) days in the hospital. Moreover, during their lifetime, OI patients go through a median of 2 (IQR 1.1–4.0) ambulatory surgeries and 1.9 (IQR 1.0–3.0) surgeries requiring hospitalisation.

The clinical pathway followed by paediatric and adult OI patients in Spain has been described by the experts as presented in Fig. 3. The main medical specialties responsible for patient management are paediatrics, endocrinology, rheumatology, traumatology, internal medicine and genetics. The diagnosis and management of paediatric and adult patients, although similar in many aspects, present some differences. Regarding pharmacological treatment, paediatric patients are mainly prescribed calcium and vitamin D supplementation and bisphosphonates. In addition to this, adult patients also receive analgesics for chronic pain and can be prescribed off-label monoclonal antibodies. The most common non-pharmacological treatment was, hearing aids, used to address premature hearing loss due to OI mainly used in adults with OI. Finally, in terms of follow-up, paediatric patients undergo more frequent tests and follow-up visits (3 visits a year), when compared with adults (2 visits a year).

Patient pathway of OI patients in Spain. Footnote: *Qualitative comments made by the CEWG to complete the patient pathway of OI patients in Spain

A majority (91%) of experts follow clinical guidelines, consensus documents or specific hospital protocols for OI management. Genetic testing is available in approximately 79% of hospitals and patients are referred to other centres if unavailable. Regarding the key factors driving early diagnosis of OI, the CEWG agreed that these include the awareness of the main signs and symptoms, availability of referral criteria and the coordination between medical specialties. In addition, according to the experts, the median age at diagnosis of OI patients is 3.8 (IQR 1.7–5.0) years-old for paediatric and 17.3 (IQR 6.0–30.0) years-old for adult patients. A median of 40% (IQR 25.0%—90.0%) of the adult patients have been diagnosed during childhood.

According to experts, 70% (IQR 50.0%—81.8%) and 50% (IQR 30.0%—63.0%) of patients are prescribed pharmacological (excluding calcium and vitamin D received by all patients) and non-pharmacological treatments, respectively. The rate of bisphosphonate use is similar in adult (70%, IQR 50.0%—80.0%) and paediatric (75%, IQR 60.0%—100.0%) patients.

Most experts (80%) transition OI patients from the paediatric to the adult specialist at the age of 18. The majority of experts (82%) interact with the paediatric/adult specialist during the transition. Experts considered that the existence of OI units where paediatric and adult specialists can interact is key to optimise patient transition. According to the panel, only 2 hospitals in Spain have officially institutionalised OI units, while some others may have units for the management of bone metabolism pathologies, or multidisciplinary teams which are not officially instituted in the hospital.

All participants (100%) considered that there are relevant unmet needs in OI. The panel agreed that the most relevant unmet need is the availability of a treatment that it is either curative or helps with symptom management. Secondly, experts considered multidisciplinary management and referral centres as relevant unmet needs, followed by the availability of consensus documents for the management of OI patients. Table 4 shows the most relevant unmet needs in OI in Spain, prioritised based on the opinion of the experts participating in the study.