Delineating and meeting the health needs of adult survivors of childhood-onset conditions is a growing quality-of-care issue. Based on estimates of those living with OI in the US ranging from 25,000  to 50,000 , approximately 3 % of the total US OI population completed the OI ANHI survey. This number is especially impressive given the fact that adults with OI are a rare, geographically dispersed population and that we recruited respondents in an incentive-free manner. In doing so, we have demonstrated how persons with rare (and not so rare) conditions can collectively address some of their important health related concerns as a virtual community.
Demographics and medical/lifestyle information
BMI exceeded the WHO diagnostic threshold for obesity (30 kg/m2) in 36 % of respondents and an additional 31 % were overweight. While this prevalence is similar to the general adult US population, it is unclear that this finding conveys the same health risk for an individual whose height is 5 or more SDs below average. Hypertension has been reported to be more prevalent in adults with OI but this was not the case in our population. Unexpectedly, adults with self-reported severe OI reported substantially less catamenial bleeding than those reporting mild or moderate disease. Heightened vigilance for cutaneous trauma or the protective effect of a wheelchair might explain the former but could not account for the latter. While vague, the large number of respondents reporting numbness suggests the need for further inquiry as the incidence of basilar invagination, a potential explanation for numbness, is much higher in persons with OI than the general population.
Neither age nor number of health care providers seen varied by self-reported OI severity grouping. The finding regarding age was surprising as we anticipated that those individuals with more severe forms of OI would be younger because of the higher number of medical and musculoskeletal problems that can accompany more severe disease. While those with the milder types of OI, such as types I and IV, can anticipate a normal lifespan, prior research has found a reduced lifespan for those with type III OI [12, 41].
The findings that age does not vary on the basis of the subjective self-reported grouping and that height is an inconsistent predictor of quality of life suggest the same outcome: there are important aspects of OI severity and functioning not captured by some of the markers relied upon in the past, including age and height. These inconsistencies underscore the need to validate the PROMIS® instruments for use in OI and to develop disease-specific QoL measures in order to better assess functioning in adults with OI. Satisfaction with sexual activity was the only construct that revealed statistically significant differences between groups.
We determined significant differences in exercise engagement based on perceived disease severity. This finding deserves further inquiry. Given that this was a self-reported disease severity rating rather than Sillence classification, do adults who report more severe OI indeed abstain from physical activity because of the severity of their condition or are there individuals with more mild forms of OI reporting greater OI severity because their condition has potentially also worsened from exercise abstinence? Previous research among adults with OI determined a correlation between decreased physical function and ability to participate in the physical actions of climbing stairs and going for walks . Similarly, a study among pediatric patients with OI found that walking ability suffered with greater OI disease severity . Such research suggests that physical activity participation is not only a challenge in OI, but also becomes less likely with augmented OI severity.
However, physical activity, especially physiotherapy involving muscle strengthening, is an important aspect of OI management  and physical activity has been shown to improve functioning in pediatric populations with mild to moderate OI . Unfortunately there are no studies to guide persons with severe OI. In light of our finding that adults with self-reported, severe OI show greater disengagement from exercise, future studies should examine this association and its determinants. In turn, longitudinal research should examine the potentially protective effect of exercise by all types of OI disease severity.
Organ-specific quality of life concerns
Adult OI respondents indicate that musculoskeletal and auditory issues have a greater impact on current and anticipated future QoL than other organ system concerns, and express even greater concern about the future impact of endocrine and pulmonary issues on QoL. Respiratory failure is a leading cause of death in severe OI [12, 41]. The lungs are often greatly affected in OI, with challenges such as pulmonary restrictive disease due to chest wall or pulmonary collagen abnormality, airway obstruction, pulmonary hypertension, and sleep apnea . Care recommendations have been developed by Sandhaus, which include intensive, longitudinal follow-up of pulmonary function in patients with OI . This is particularly important given the high rates of sedentarism and elevated BMI reported [12, 45]. Therefore, the low rate of reported pulmonary consultation could be an opportunity for improving care and health status.
Up to 50 % of adults with OI have dentogenesis imperfecta  yet approximately one-third of our respondents reported no regular dental care, and 74 % expressed current QoL concerns regarding their dental health. An important future research direction should include a more in-depth analysis of dental care in OI to establish whether adults with OI have difficulty gaining access to dental care or whether there is another explanation for this shortfall.
Multiple insights into improving research and care were gleaned from the ROS. Results from the QoL portion of the medical ROS revealed that adults with OI have future-related QoL concerns with organ systems identified as troublesome, particularly the musculoskeletal, auditory, and pulmonary subsystems. In addition, respondents expressed future-related, QoL concerns with the endocrine and gastrointestinal organ systems, subsystems that have not been heavily studied in the existing OI literature. For better incorporation of patients’ concerns into care and integration of what doctors know to be important with what matters to patients, exploration of the endocrine and gastrointestinal subsystems represents an important future research direction.
Patient-centered/patient-reported outcomes: PROMIS®
As according to PROMIS®, adults with OI report lower general physical health status than the general population. General physical health status among respondents reporting the greatest disease severity was lower, but the clinical significance of this finding is uncertain. Numerous statistically significant differences exist among adults with OI of varying severity as well as between adults with OI and the general population, but the clinical significance of these differences is uncertain. Indeed, the PROMIS® instruments suggest that, overall, the OI community does not differ greatly from the general population. Moreover, the results of the OI-ANHI survey support previous findings that adults with OI report a high level of life satisfaction in spite of a significant disease burden which, in our collective experience, the authors would characterize as resilience [7, 8, 46].
We and others have shown significant correlations between disease severity and height Z-score , but when PROMIS® T-scores are segregated by quartile of height Z-score, our results suggest that these measures may convey slightly different QoL information in this population. Clinicians encounter adults with ostensibly mild OI who consider their condition to be severe when their only objective manifestation of OI is adult-onset deafness. Perhaps “severity” should also be viewed from the patient’s perspective and not only by height Z-score or Sillence type. Whether nuances in QoL information conveyed by these different measures are important is unknown but, if so, they could be relevant to the development of a disease-specific QoL instrument for OI. The PROMIS® scales are validated and scaled for a healthy, adult population, which represents a challenge in their application to a chronic, rare disease group. Although our results suggest that adults with OI exhibit similarities with the normative population, it is possible that the scales are not capturing some differences within our sample. The validation of PROMIS® instruments for persons with OI will be an important future study focus so that researchers can better understand QoL in OI and move towards the application of PROs both in clinical settings and comparative effectiveness research .
Most likely, our recruitment and web-based strategies resulted in a self-selection/enrollment bias. We were likely unable to capture the responses of non-Internet users in this study. Nonetheless, our study represents the first effort to query a large sample of adults with OI regarding their disease burden and QoL. Although our study relied heavily on an Internet rather than a paper format, several studies have quantified the reliability of Internet research studies by comparing them to identical studies conducted with non-internet formats and have found them to be equally as reliable [48, 49]. Internet methods have been shown to be as reliable as paper formats when measuring patient-reported health outcomes for those suffering from chronic health conditions .
Our results may be limited by the restricted demographic heterogeneity of our sample. Male gender, lower educational achievement status, and non-Caucasian race were all under-represented. Previous research has shown that women generally rely on the Internet for health and medical information more than men . In addition, as of 2015, those with college education are more likely than those who do not have high school diplomas to use the Internet and the minority groups of African American and Hispanic ancestry are less likely to be Internet users than Caucasians . These noted differences in Internet usage may partially explain why our sample proved to be predominantly female, well educated, and Caucasian. However, previous studies examining OI have also noted a higher proportion of female [7, 8, 38], more highly educated , Caucasian  respondents, (the majority of whom describe themselves as having type I OI) . Multiple other studies have also reported a middle-aged mean [7, 8, 45]. Thus, our study accessed those members of the OI community most often reported in other research studies. One of our future goals is to reach the populations under-represented in this study, namely men, minorities, and those with a lower level of education.
Another limitation of this study was the challenge of defining disease severity. Even before Sillence developed the current OI classification in 1979, efforts to stratify disease severity had been ongoing and continue to be a challenge because of the expanding clinical and genetic heterogeneity found by researchers. At present, 17 different genetic causes of OI have been identified  and it is anticipated that more will be elucidated. Therefore, the effort to define disease severity is a continuous struggle in OI research. Furthermore, misclassification of OI type was possible due to the self-report nature of our research. Indeed, 31 % of respondents were unaware of their Sillence type, and twelve respondents characterized their OI as both Type II and mild, which, until recently, was considered lethal.
In this study, however, we attempted to focus less on Sillence classification, as our goal was greater inclusion of the patient’s perspective and his or her own assessment of functioning and disease burden. Indeed, it has been documented that physicians and patients sometimes disagree on disease severity in chronic diseases. Lack of concordance between physician and patient ratings of disease severity in rheumatoid arthritis is an apt example [54, 55]. Therein, we developed the severity measure for this study in a self-report format. Yet, objective measures of OI severity were not absent from our work. Rather than rely fully on Sillence classification, we included height as an objective marker of disease severity and then examined its relationship with both self-reported disease severity as well as the PROMIS® instruments.
Chief among the study’s strengths is the very large number of respondents and the PCO perspective of this inquiry. The success of this survey in reaching a large number of adults with OI has encouraged our research team to explore new strategies to engage the groups that were underrepresented in the survey, namely men, persons of limited educational achievement, and non-Caucasians.