Initial report of the osteogenesis imperfecta adult natural history initiative

Abstract

Background: A better understanding of the natural history of osteogenesis imperfecta (OI) in adulthood should improve health care for patients with this rare condition.

Methods: The Osteogenesis Imperfecta Foundation established the Adult Natural History Initiative (ANHI) in 2010 to give voice to the health concerns of the adult OI community and to begin to address existing knowledge gaps for this condition. Using a web-based platform, 959 adults with self-reported OI, representing a wide range of self-reported disease severity, reported symptoms and health conditions, estimated the impact of these concerns on present and future health-related quality of life (QoL) and completed a Patient-Reported Outcomes Measurement Information System (PROMIS®) survey of health issues.

Results: Adults with OI report lower general physical health status (p < .0001), exhibit a higher prevalence of auditory (58% of sample versus 2-16% of normalized population) and musculoskeletal (64% of sample versus 1-3% of normalized population) concerns than the general population, but report generally similar mental health status. Musculoskeletal, auditory, pulmonary, endocrine, and gastrointestinal issues are particular future health-related QoL concerns for these adults. Numerous other statistically significant differences exist among adults with OI as well as between adults with OI and the referent PROMIS® population, but the clinical significance of these differences is uncertain.

Conclusions: Adults with OI report lower general health status but are otherwise more similar to the general population than might have been expected. While reassuring, further analysis of the extensive OI-ANHI databank should help identify areas of unique clinical concern and for future research. The OI-ANHI survey experience supports an internet-based strategy for successful patient-centered outcomes research in rare disease populations.

Fig. 1

Histogram displaying age distribution for all respondents

Fig. 2

Histogram depicting age in five-year groups by self-reported severity grouping. Three categories of severity are reported: mild, moderate, and severe

Fig. 3

Box plot representing self-reported OI severity and NHANES-III Z-score for height. The diamonds represent the mean and the horizontal lines within the box the median height Z-score. The upper and lower bounds of the box represents the 75^th and 25^th percentile for height Z-score respectively. The whiskers represent the minima and maxima height Z-score values and open circles represent outliers

Fig. 4

Histogram displaying number of healthcare providers seen for all respondents

Fig. 5

Histogram depicting engagement in or disengagement from exercise by self-reported severity grouping. A response of “1” correlates with “yes” for exercise while “0” represents a response of “no.” Three categories of severity are reported: mild, moderate, and severe

Fig. 6

The impact of specific organ system concerns on current and anticipated future QoL for all respondents (left) and for those already experiencing problems within that organ system (right) described using a 5-point Likert scale ranking of organ-system-based concerns from least (1) to greatest (5) impact on current and anticipated future quality of life

Fig. 7

Mean PROMIS® T-scores with 95% confidence limits by self-reported OI severity. Symbols represent self-reported OI severity (▲ = mild, ■ = moderate, ● = severe). The mean T-scores of the PROMIS® referent population are indicated by the solid vertical reference line placed at “50”. Therefore, symbols to the right of the reference line are higher than the PROMIS® population mean (i.e. more of that construct than the PROMIS® population) and symbols to the left of the reference line are lower than the PROMIS® population mean (i.e. less of that construct than the PROMIS® population). p-values are for the comparisons of T-scores within disease severity strata amongst the entire OI cohort (left column, “OI severity”) and between the entire OI cohort and the general PROMIS® population (right column, “Population”)

Fig. 8

Mean PROMIS® T-scores with 95% confidence limits by quartile of NHANES-III Z-score for height. Symbols represent self-reported OI severity (▲ = mild, ■ = moderate, ● = severe). The mean T-scores of the PROMIS® referent population are indicated by the solid vertical reference line placed at “50”. Therefore, symbols to the right of the reference line are higher than the PROMIS® population mean (i.e. more of that construct than the PROMIS® population) and symbols to the left of the reference line are lower than the PROMIS® population mean (i.e. less of that construct than the PROMIS® population). p-values are for the comparisons of T-scores within disease severity strata amongst the entire OI cohort (left column, “OI severity”) and between the entire OI cohort and the general PROMIS® population (right column, “Population”)