The expert team and focus groups expressed the need to address all aspects of bone fractures. Incidence, healing and type of treatment, as well as the mechanism of fracture (low impact vs high impact) in children will be reported. Incidence will be reported as the sum of clinically reported fractures, patient reported fractures and radiologically confirmed fractures, considering that not all fractures are always clearly visible on radiologic imaging. In daily practice, many patients are treated for clinical fractures without radiologic imaging or will manage minor fractures themselves without hospital visits and minimize the exposure to radiation.
The focus groups defined surgeries as major life events in the majority of cases, as the severity of the disease and the quality of healthcare was determined by the complexity and frequency of surgery and the outcome. The expert team decided to record these events.
Bone mineral density (BMD)
BMD, measured with Dual-Energy X-ray Absorptiometry scan (DXA-scan), is currently widely used as a substitute parameter for bone quality in OI and monitoring of medical treatment. Therefore a DXA-scan was selected as the preferred outcome measurement, despite its shortcomings of not taking into account altered body shape and the lack of a linear correlation to the fragility of the bones .
The expert team agreed to include the measurement of scoliosis and kyphosis with Cobb angles on total spine X-rays as spinal deformities are common in OI and severe malformations of the spine may lead to various other problems affecting quality of life.
The Beighton Score was selected to measure joint laxity during growth . As laxity does not change in adulthood the Beighton Score will only be measured once at baseline.
Given the frequency of malalignment, the relation between bowing and fractures, the possibility for guided growth, and the need for surgery to improve function if significant malalignment is present, the expert team chose long standing axis X-rays to measure and report on limb alignment.
Short stature and growth
Physical appearance was considered an important issue during the focus group sessions, however no clinician or patient reported rating was found. Growth and stature by measuring height was determined to be the best way to express and monitor this domain.
Upper limb function
For the measurement of upper limb function and its impact on independence in daily life, the PROMIS Ped—upper extremity and PROMIS—upper extremity for adults were selected for children and adults . Other PROMs and other COMs were felt to be too extensive for screening (e.g. ABILHAND-Kids, Bayley Scales of Infant Development, Peabody Developmental Motor Scales) or were not applicable to the majority of people with OI (e.g. the Brief Assessment of Motor Function (BAMF)).
Lower limb function
Measurement instruments from the literature search as well as those instruments suggested by the experts resulted in a choice of more than 30 instruments. There was consensus on using a combination of PROMs and COMs to describe clinical assessment as well as “real life” performance. Whilst feedback on the PROMIS Ped—mobility module to measure lower limb function was conclusive in the 2nd Delphi round, the choice of COM was not. The Gillette FAQ, BAMF, FMS, the timed up and go test and the 6 min, 1 min and 30 s walking tests were all discussed as possible options. The 30 s walking test was selected by the experts for both children and adults. It is the least burdensome, allows some measurement of progression and gives an outcome when walking is present . For classifying functional mobility, the FMS was chosen for children, as it records the range of assistive devices a child may use and therefore provides information on the different assistive devices used in different environments .
For adults there was a good level of support among the experts for the PROMIS—physical functioning module as the PROM and the 30 s walking test as the COM.
Age is a determining factor in this domain as adults have different goals in self-care compared to young children. For children the Functional Independence Measure for children (WeeFIM), PODCI, PedsQL, and PROMIS were discussed. As a relatively small percentage of children with OI have issues with self-care, (often due to upper extremity issues) the expert team concluded that screening for self-care problems in children could be addressed in the core set of measurements. Therefore, the expert team chose the PROMIS—upper limb module as screening instrument instead of the more detailed but time-consuming WeeFIM tool. If indicated, more specific instruments tailored to measure self-care skills are available.
In adults, the SF-36, PROMIS—upper extremity module and the Sunnaas index of ADL (SI)
were considered. The expert team felt that a more extensive self-care assessment was warranted for adults. As such, the SI was chosen over the SF-36 (with only one item on self-care) to complement the PROMIS—upper extremity module [15, 22].
Quality of life
The focus groups reported pain as an important issue for individuals with OI as it affects daily life, mobility, participation, work life and social relationships. Pain was subdivided by the focus groups into acute pain such as in the case of fractures and chronic/persevering pain. Based on the strong support for PROMIS modules overall and no clear preference between PROMIS Ped—pain interference, PODCI and PedsQL, the expert team chose the PROMIS Ped—pain interference for children in the final outcome set. For pain intensity in children, the colored visual analog pain scale  was selected. In adults, both PROMIS—pain interference and pain intensity subscales were selected after the first 2 Delphi rounds.
The adult focus groups indicated fatigue was a notable problem, and it was also referenced in the child focus groups. For children, PROMIS Ped—fatigue as measurement tool was strongly preferred over PedsQL and PODCI.
For adults, the SF-36 vitality scale and PROMIS—fatigue remained after 2 Delphi rounds. Finally, the PROMIS—fatigue was chosen based on the strong support for the PROMIS modules overall .
Psychosocial issues are more prominent in OI compared to other disabilities . Emotional well-being is a broad concept, which needed to be specified for the OI population. The expert team as well as the focus groups agreed on the importance of anxiety and mood. PROMIS Ped, PedsQL and PODCI contain some subscales covering emotional well-being. In the 2nd Delphi round there was a slight preference for using the PROMIS Ped scales and in the fourth Delphi round there was full agreement on using the PROMIS Ped—emotional distress anxiety and depression subscale to cover emotional well-being.
For adults the 3rd Delphi round resulted in strong support for the PROMIS—anxiety and depression subscales. The SF-36 (Emotional role functioning and mental health), the WHO QOL-BREF as well as the HADS were also subject to discussion but garnered low support in the first and second Delphi round.
Again, the PROMS PedsQL, PODCI and PROMIS Ped were suggested as the best options for the screening of social functioning in children with OI. Despite the PedsQL already being conclusive for social functioning in the first Delphi round, the final Delphi round resulted in agreement on the use of PROMIS Ped scales for all domains with PROMIS Ped -peer relationships replacing the PedsQL for social functioning.
For adults the SF-36, WHO Quality of Life—BREF (WHO QOL-BREF) social relationships, Female Sexual Functioning Index (FSFI), International Index of Erectile Function (IIEF), PROMIS—ability to participate, PROMIS—sexual function and satisfaction measures were all discussed. The PROMIS—ability to participate had strong support in the first Delphi round and the PROMIS—sexual function and satisfaction measures were added in the second Delphi round.
The focus groups as well as the expert group agreed that social functioning and participation are equally important and both items were retained. For children it was difficult to find an instrument for participation, which was not too time-consuming. While there was a preference to use the PROMIS Ped scales when possible, the school subscale of the PedsQL was optimal for participation and was selected . Participation is also embedded in the PODCI but cannot be easily retrieved as a separate subscale.
For adults, participation is measured by the PROMIS—ability to participate in social roles and activities (already chosen to measure social functioning) as well as the PROMIS—satisfaction with social participation. Both had high support in the 2nd Delphi round. The SF-36 -Mental Health domain—social function, was found to be less suitable in the 2nd Delphi round.