Psychosocial Outcomes of Pain and Pain Management in Adults with Osteogenesis Imperfecta: A Qualitative Study.

Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility and fractures, short stature, dental abnormalities, hearing loss, scoliosis, and chronic pain. Despite a growing literature on the functional outcomes of OI, limited research has explicitly examined the psychosocial outcomes of pain within OI. Adults with OI (N = 15) were interviewed to understand pain-related experiences through a thematic analysis of semi-structured interview data. Research team members, genetic research experts, and OI clinicians developed an interview guide focused on topics related to pain and mental health challenges. Participants' transcripts were coded by two independent coders; codes were then merged across coders and quotation outputs were subsequently abstracted (paraphrased then thematically classified) to identify common themes. Themes related to pain management variability regarding pain type, pain risk management and accessibility, pain outcomes (e.g., behavior, cognitive, affective), and pain exacerbating factors (e.g., individual, contextual) were identified. Participants reported chronic and acute pain, and despite the inaccessibility and stigmatization of pain medications (e.g., opioids), pharmacological treatments were the most common pain management approach. Participants reported negative pain outcomes, such as limited daily functioning and activity participation, fear, anger, anxiety, depression, and difficulty concentrating. Lastly, participants suggested that lack of physician and community knowledge on chronic pain in OI indirectly exacerbates both subjective pain intensity and outcomes. Although limited by a small, nondiverse sample, the current study provides valuable exploration of the unique pain experiences of adults with OI that may have implications for proactive management, treatment development, and clinician training.

Comparison of faculty and student perceptions of sexual and gender minority content in a preclerkship medical curriculum.

BACKGROUND: Sexual and gender minority (SGM) persons experience stark health disparities. Efforts to mitigate disparities through medical education have met some success. However, evaluations have largely focused on subjective perspectives rather than objective measures. This study aimed to quantify Boston University School of Medicine's sexual and gender minority (SGM) education through surveys of course directors (CDs) and medical students regarding where SGM topics were taught in the preclerkship medical curriculum. Responses were compared to identify concordance between faculty intention and student perceptions regarding SGM education. METHODS: A cross-sectional survey was distributed to preclerkship CDs and current medical students in Spring 2019 and 2021, respectively, regarding where in the mandatory preclerkship curriculum CDs deliberately taught and where first- and second-year students recalled having learned 10 SGM topic domains. RESULTS: 64.3% of CDs (n = 18), 47.0% of the first-year class (n = 71), and 67.3% of the second-year class (n = 101) responded to the surveys. Results indicate that, as anticipated, deliberate SGM teaching correlates with greater student recall as students recalled topics that were reported by CDs as intentionally taught at a significantly higher rate compared to those not intentionally taught (32.0% vs. 15.3%; p < 0.01). Students most commonly recalled learning SGM-related language and terminology, which is likely partly but not entirely attributed to curricular modifications and faculty development made between distribution of the faculty and student surveys, indicating the importance of all faculty being trained in appropriate SGM terminology and concepts. Discordance between faculty intention and student recall of when topics were taught reveals opportunities to enhance the intentionality and impact of SGM teaching. CONCLUSIONS: Students perceive and recall SGM content that is not listed as learning objectives, and all faculty who utilize this material in their teachings should receive foundational training and be thoughtful about how information is framed. Faculty who intentionally teach SGM topics should be explicit and direct about the conclusions they intend students to draw from their curricular content.

Complications and Revisions After Spine Surgery in Patients With Skeletal Dysplasia: Have We Improved?

STUDY DESIGN: Retrospective case series. OBJECTIVE: To report contemporary rates of complications and subsequent surgery after spinal surgery in patients with skeletal dysplasia. METHODS: A case series of 25 consecutive patients who underwent spinal surgery between 2007 and 2017 were identified from a single institution's skeletal dysplasia registry. Patient demographics, medical history, surgical indication, complications, and subsequent surgeries (revisions, extension to adjacent levels, or for pathology at a non-contiguous level) were collected. Charlson comorbidity indices were calculated as a composite measure of overall health. RESULTS: Achondroplasia was the most common skeletal dysplasia (76%) followed by spondyloepiphyseal dysplasia (20%); 1 patient had diastrophic dysplasia (4%). Average patient age was 53.2 ± 14.7 years and most patients were in excellent cardiovascular health (88% Charlson Comorbidity Index 0-4). Mean follow up after the index procedure was 57.4 ± 39.2 months (range). Indications for surgery were mostly for neurologic symptoms. The most commonly performed surgery was a multilevel thoracolumbar decompression without fusion (57%). Complications included durotomy (36%), neurologic complication (12%), and infection requiring irrigation and debridement (8%). Nine patients (36%) underwent a subsequent surgery. Three patients (12%) underwent a procedure at a non-contiguous anatomic zone, 3 (12%) underwent a revision of the previous surgery, and another 3 (12%) required extension of their previous decompression or fusion. CONCLUSIONS: Surgical complication rates remain high after spine surgery in patients with skeletal dysplasia, likely attributable to inherent characteristics of the disease. Patients should be counseled on their risk for complication and subsequent surgery.

Novel missense ACAN gene variants linked to familial osteochondritis dissecans cluster in the C-terminal globular domain of aggrecan.

The cartilage aggrecan proteoglycan is crucial for both skeletal growth and articular cartilage function. A number of aggrecan (ACAN) gene variants have been linked to skeletal disorders, ranging from short stature to severe chondrodyplasias. Osteochondritis dissecans is a disorder where articular cartilage and subchondral bone fragments come loose from the articular surface. We previously reported a missense ACAN variant linked to familial osteochondritis dissecans, with short stature and early onset osteoarthritis, and now describe three novel ACAN gene variants from additional families with this disorder. Like the previously described variant, these are autosomal dominant missense variants, resulting in single amino acid residue substitutions in the C-type lectin repeat of the aggrecan G3 domain. Functional studies showed that neither recombinant variant proteins, nor full-length variant aggrecan proteoglycan from heterozygous patient cartilage, were secreted to the same level as wild-type aggrecan. The variant proteins also showed decreased binding to known cartilage extracellular matrix ligands. Mapping these and other ACAN variants linked to hereditary skeletal disorders showed a clustering of osteochondritis dissecans-linked variants to the G3 domain. Taken together, this supports a link between missense ACAN variants affecting the aggrecan G3 domain and hereditary osteochondritis dissecans.

Patient-reported prevalence of gastrointestinal issues in the adult skeletal dysplasia population with a concentration on osteogenesis imperfecta.

Patient-reported concerns indicate that gastrointestinal (GI) manifestations affect the skeletal dysplasia population, but quantitative information regarding prevalence and severity of GI issues is limited. We examined the frequency and characteristics of GI symptoms in adults with skeletal dysplasias by reviewing 101 responses to the Gastrointestinal Symptom Rating Scale (GSRS). Participant demographics, medication history, and ambulatory status were collected from medical records. Compared to published GSRS reference data, our cohort scored higher on reflux, diarrhea, and total scores, and lower on abdominal pain and indigestion scores; none of these differences were statistically significant. Although osteogenesis imperfecta respondents had more severe symptoms across all domains, only reflux reached significance (p = 0.009). Scores in patients with achondroplasia were higher for indigestion, constipation, diarrhea, and total scores and lower on abdominal pain and reflux scores than the general population; only the diarrhea score was significant (p = 0.034). There were no statistically significant differences in any of the domain or total GSRS scores across ambulatory status groups. Increased height correlated with worse abdominal pain domain score (p = 0.033). The number of medications positively correlated with total GSRS score (p = 0.013). Future studies should include larger numbers of individuals to allow a more in-depth analysis of patient-reported symptoms and signs within this population.

Infrared Spectroscopy-Determined Bone Compositional Changes Associated with Anti-Resorptive Treatment of the oim/oim Mouse Model of Osteogenesis Imperfecta.

Applications of vibrational spectroscopy to assess bone disease and therapeutic interventions are continually advancing, with tissue mineral and protein composition frequently investigated. Here, we used two spectroscopic approaches for determining bone composition in a mouse model (oim) of the brittle bone disease osteogenesis imperfecta (OI) with and without antiresorptive agent treatment (alendronate, or ALN, and RANK-Fc). Near-infrared (NIR) spectral analysis using a fiber optic probe and attenuated total reflection Fourier transform infrared spectroscopy (ATR FTIR) mode were applied to investigate bone composition, including water, mineral, and protein content. Spectral parameters revealed differences among the control wildtype (WT) and OIM groups. NIR spectral analysis of protein and water showed that OIM mouse humerii had ∼50% lower protein and ∼50% higher overall water content compared to WT bone. Moreover, some OIM-treated groups showed a reduction in bone water compared to OIM controls, approximating values observed in WT bone. Differences in bone quality based on increased mineral content and reduced carbonate content were also found between some groups of treated OIM and WT bone, but crystallinity did not differ among all groups. The spectroscopically determined parameters were evaluated for correlations with gold-standard mechanical testing values to gain insight into how composition influenced bone strength. As expected, bone mechanical strength parameters were consistently up to threefold greater in WT mice compared to OIM groups, except for stiffness in the ALN-treated OIM groups. Furthermore, bone stiffness, maximum load, and post-yield displacement showed the strongest correlations with NIR-determined protein content (positive correlations) and bound-water content (negative correlations). These results demonstrate that in this study, NIR spectral parameters were more sensitive to bone composition differences than ATR parameters, highlighting the potential of this nondestructive approach for screening of bone diseases and therapeutic efficacy in pre-clinical models.

A Novel Curriculum Assessment Tool, Based on AAMC Competencies, to Improve Medical Education About Sexual and Gender Minority Populations.

PROBLEM: Medical education aspires to mitigate bias in future professionals by providing robust curricula that include perspectives of and practices for caring for sexual and gender minority (SGM) populations; however, implementation of these ideals remains challenging. Medical school leaders motivated to improve curricula on caring for SGM populations must survey their school's current curricula to identify strengths and opportunities for improvement. In 2014, the Association of American Medical Colleges (AAMC) published 30 SGM competencies that curricula should address. Here the authors describe the development of a tool to efficiently assess whether an undergraduate medical education (UME) curriculum adequately incorporates the AAMC-recommended SGM competencies. APPROACH: In 2018, Boston University School of Medicine (BUSM) convened a group of faculty and students with experience and expertise regarding SGM health. The group distilled the 30 AAMC competencies into 12 SGM topic areas that should be addressed in any UME curriculum, and they developed a curriculum assessment tool to evaluate the presence and timing of these topic areas in the BUSM curriculum. This tool was distributed to all course and clerkship directors responsible for the required UME curriculum at BUSM to investigate where these topic areas are addressed (May-June 2019). OUTCOMES: The curriculum assessment tool identified several strengths in the preclerkship and clerkship curricula, including faculty willingness and enthusiasm to include SGM content. The assessment tool also revealed that some SGM topic areas are underrepresented in the BUSM curriculum, particularly during clerkships. NEXT STEPS: The curriculum assessment tool described here is a straightforward, standardized instrument to map SGM topic areas within any UME curriculum. It is designed to be comprehensible by individuals who are not familiar with SGM health. The tool minimizes barriers to medical curricular change by providing a mechanism to assess and understand how SGM health is incorporated into existing curricula.

Orthopedic considerations and surgical outcomes in Ehlers-Danlos syndromes.

The Ehlers-Danlos syndromes (EDS) are a clinically and genetically heterogeneous group of connective tissue disorders with varying physical manifestations. There are no clear guidelines for addressing orthopedic concerns or reporting surgical outcomes in this population. This article reviews the literature, reports on a new study, and offers considerations prior to surgical intervention. The new study seeks to determine the effectiveness of surgical intervention in individuals with EDS. It is a retrospective chart review of 154 individuals clinically diagnosed with EDS who had orthopedic surgery >2 years ago at Hospital for Special Surgery. A total of 120 individuals were included in the study. One hundred eleven females and 9 males underwent a total of 320 orthopedic surgeries, of which 204 surgeries had available post-operative follow-up. The average age at surgery was 38.2 years (range: 7.6-83.3). Multiple post-operative complications (290) were reported in 91% of cases. Common complications were persistent pain/discomfort (45), continued subluxation/dislocation (20), instability (19), pain/discomfort from hardware (17), and infection (16). Our results suggest that surgical outcomes are worse for individuals with EDS compared to the general population, a finding which is similar to other studies. Complications occurred more frequently in the EDS population than the average population, suggesting that surgery should be undertaken by a multidisciplinary team of clinicians with careful pre-operative planning and full knowledge of the risks and benefits. Guidelines for the care of this unique population must be established.

Presurgical Laser Hair Removal: Protocoling a Safe and Effective Procedure for Transgender Patients.

Purpose: For transgender (TG) women preparing to undergo neovaginoplasty, multidisciplinary care is essential, with physicians working together to ensure timely, complete, and cost-effective treatment. Methods: The protocol was developed through the clinical experience with >30 patients for preneovaginoplasty laser hair removal (LHR). Results: This report details the procedure used at an academic medical center for preneovaginoplasty genital LHR. Although treatment must often be individualized, methods as described for evaluation and treatment of presurgical hair have been successfully used in >30 patients. Conclusion: Given the limited available literature regarding this topic, it is our hope that this report will encourage other centers to offer safe and effective presurgical genital LHR to TG patients.

Quality of life in adults with achondroplasia in the United States.

Studies examining quality of life (QoL) in adults with achondroplasia are limited. We report on QoL and psychiatric illness diagnoses in a modern cohort of adults with achondroplasia. SF-36 Health Survey scores from adults with achondroplasia were compared to general population scores. Demographics, physical measurements, and psychiatric illness diagnoses were recorded from medical records. The achondroplasia population had lower scores than the general population in all categories. Most people with achondroplasia (56%) had a diagnosed psychiatric illness. Those with a diagnosed psychiatric illness had lower scores in physical functioning, role limitations due to physical and emotional health, and mental health. Pain, energy/fatigue, and general health scale scores were roughly equivalent (<2 points difference). Social functioning was >15 points higher in individuals with psychiatric illness diagnoses. Adults with achondroplasia report significantly lower physical and mental well-being and had nearly 3× the rate of psychiatric illness diagnosis than the general population, highlighting the importance of total care for this population. Healthcare providers must understand the physical and mental comorbidities of achondroplasia, beyond short stature and orthopedic issues, so they can proactively improve QoL across the lifespan for patients and families.

Respiratory impairment impacts QOL in osteogenesis imperfecta independent of skeletal abnormalities.

Respiratory insufficiency is the leading cause death in people with osteogenesis imperfecta (OI). Adults with OI reported that respiratory symptoms negatively impacted psychosocial wellbeing and limited daily physical activities, irrespective of OI type, age, stature, or scoliosis. The impact of respiratory status on quality of life in this population warrants further investigation. PURPOSE: Respiratory insufficiency is the leading cause of mortality in osteogenesis imperfecta (OI), a heterogeneous group of heritable connective tissue disorders characterized by fractures, bone fragility, and scoliosis. There is little research on how respiratory health influences daily life in this population. This study explores the relationship between respiratory function and quality of life in adults with OI. METHODS: One hundred fifty-seven adults with OI completed the St. George's Respiratory Questionnaire (SGRQ) and provided demographic and health information through REDCap. SGRQ scores were compared to reference scores for the general population, and comparisons were made between OI type, presence of scoliosis, stature, and other factors such as age or comorbidities. RESULTS: Average age was 45.87 years (range 19-81). Respondents scored worse on average (32 ± 23) than the normative data (6 ± 1). Those with type I OI scored better than those with type IV (p = 0.002) or type III (p = 0.024). Total scores correlated with age, activity level, assistive device use, and presence of pulmonary or cardiac comorbidities but did not correlate with stature or degree of scoliosis. CONCLUSION: Respiratory symptoms negatively impact both psychosocial wellbeing in the OI population and limit daily physical activity. These limitations occur irrespective of their OI type, age, stature, or scoliosis and reflect the dramatic impact of respiratory status on quality of life for people with OI. Future studies should examine the etiology of respiratory insufficiency in this population so guidelines for management can be established.

Cardiopulmonary Status in Adults with Osteogenesis Imperfecta: Intrinsic Lung Disease May Contribute More Than Scoliosis.

BACKGROUND: Osteogenesis imperfecta (OI) is a heterogeneous group of collagen-related disorders characterized by osteopenia, bone fractures, spine deformities, and nonskeletal complications. Cardiopulmonary complications are the major cause of morbidity and mortality in adults with OI. The cause of such problems was often attributed solely to the presence of large scoliosis curves affecting pulmonary function and, indirectly, cardiovascular health. However, recent studies suggest this may not be the case. Therefore, determining the relationships and causative agents of cardiopulmonary problems in patients with OI, specifically pulmonary impairment, is important to improving the overall wellbeing, quality of life, and survival of these patients. QUESTIONS/PURPOSES: (1) Is cardiopulmonary fitness in OI solely related to the presence of scoliosis? (2) What is the prevalence of heart and lung complications in this adult population? (3) Does the presence of pulmonary impairment impact quality of life in adults with OI? METHODS: This is a prospective observational cross-sectional study. Within 1 year, each participant (n = 30) completed pulmonary function testing, echocardiogram, ECG, chest CT, AP spine radiography, and quality-of-life assessments (SF-36, St. George's Respiratory Questionnaire, Functional Outcomes of Sleep Questionnaire, and Pittsburgh Sleep Quality Index). In terms of pulmonary function, we differentiated restrictive and obstructive physiology using the ratio of forced expiratory volume over one second to forced vital capacity (FEV1/FVC), with restrictive lung physiology defined as FEV1/FVC > 0.8 and obstructive lung physiology as FEV1/FVC < 0.7. Spine radiographs were evaluated for scoliosis. Chest CT images were reviewed to qualitatively assess the lungs. The statistical analysis involved a Kruskall-Wallis test with Bonferroni's correction and a bivariate correlation analysis using Spearman's rho correlation coefficient (p < 0.05). RESULTS: Sixteen of 23 participants with restrictive lung physiology had scoliosis; their ages ranged from 19 years to 67 years. There was no correlation between the magnitude of the scoliosis curve and deficient pulmonary function (R = 0.08; p = 0.68). Seven participants had normal pulmonary function. The average scoliosis curve was 44 ± 29°. Thirteen participants had abnormal ECG findings while 10 had abnormal echocardiogram results. All but two individuals with abnormal chest CT results were found to have bronchial wall thickening. There were no differences in pulmonary or cardiac findings between OI types, except for FVC and total lung capacity, which were lower in individuals with Type III OI than in those with other types of OI. FEV1/FVC correlated with St. George's Respiratory Questionnaire (R = 0.429; p = 0.02) but not with Functional Outcomes of Sleep Questionnaire (R = -0.26; p = 0.19) or SF-36 scores (physical component summary: R = -0.037, p = 0.85; mental component summary: R = -0.204, p = 0.29). CONCLUSIONS: The lack of a relationship between decreased pulmonary function and the severity of scoliosis suggests that restrictive lung physiology in this population is likely because of factors intrinsic to OI and not entirely because of thoracic cage deformities. The fact that pulmonary impairment influences self-perceived quality of life exemplifies how detrimental such complications may be to everyday functioning. This also reinforces the importance of determining the underlying cause of cardiopulmonary impairment in this population to set clear clinical guidelines of care. LEVEL OF EVIDENCE: Level II, prognostic study.

Joint Replacements in Individuals With Skeletal Dysplasias: One Institution's Experience and Response to Operative Complications.

BACKGROUND: Skeletal dysplasias are a heterogeneous group of >400 genetic disorders characterized by abnormal bone growth. Many individuals experience joint pain and limitation, coming to require joint replacement much earlier than the average-statured population. In addition, prosthesis survival rate is less in the dysplastic population. The purpose of this study is to identify risk factors for surgery and provide recommendations to improve surgical outcomes. METHODS: This a retrospective review of 29 individuals with a skeletal dysplasia who had 64 joint replacements between April 1985 and January 2019 at a single institution. We collected demographics, physical examination, medical history, imaging studies, surgical indication, and complications. RESULTS: Spondyloepiphyseal dysplasia was the most common skeletal dysplasia (7), followed by pseudoachondroplasia (4) and multiple epiphyseal dysplasia (4). Average age of the cohort was 40.6 years (range 14-64). Hip arthroplasty (34) was the most commonly performed surgery. The majority of arthroplasties (75%) required custom components. Complication rate was 37.3%, most commonly pulmonary embolism (3) and pneumonia (3). Most complications (81.8%) occurred in individuals with either a pre-existing cardiopulmonary comorbidity or lumbar/sacral deformity. Body mass index did not correlate with complication severity (R = -0.042, P = .752) or rate (R = 0.006, P = .963). CONCLUSION: Surgical complications are highest in patients with pre-existing cardiopulmonary conditions. Body mass index does not predict complications in this cohort. Preoperative evaluations for individuals with skeletal dysplasias should include comprehensive work-up of spine issues and extraskeletal systems that present an operative risk. Intraoperative protocol should include special consideration for placement on the table, airway maintenance, and spinal cord monitoring in select cases.

Daily Time-Place Learning in Young Children.

Pre-school children find it difficult to correctly report if it is morning or afternoon. The present study tested whether children could learn a non-verbal Time-Place Learning (TPL) task that depended on time of day. Twenty-five 4-year-olds were repeatedly asked to find a toy in one of two boxes. Children in the Cued condition were told the toy was in one box in the morning and in another box in the afternoon. Children in the Not Cued condition were told the toy was sometimes in one box and sometimes in the other box. After 80 trials, children were asked if it was morning or afternoon. About 65% of the children learned the TPL task, and about three-quarters of the children verbally identified if it was morning or afternoon. However, the children who learned the TPL task were not necessarily the children who correctly answered whether it was morning or afternoon, and those in the Cued condition were no more likely to solve the task than those in the Not Cued condition. The implication is that children have a sense of time that can be used to solve spatio-temporal contingencies, but does not depend on the verbal understanding of time of day.

Predicting Microbiome Function Across Space Is Confounded by Strain-Level Differences and Functional Redundancy Across Taxa.

Variation in the microbiome among individual organisms may play a critical role in the relative susceptibility of those organisms to infection, disease, and death. However, predicting microbiome function is difficult because of spatial and temporal variation in microbial diversity, and taxonomic diversity is not predictive of microbiome functional diversity. Addressing this issue may be particularly important when addressing pandemic diseases, such as the global amphibian die-off associated with Bd. Some of the most important factors in probiotic development for disease treatment are whether bacteria with desired function can be found on native amphibians in the local environment. To address this issue, we isolated, sequenced, and assayed the cutaneous bacterial communities of Plethodon cinereus along a gradient of land use change. Our results suggest that cutaneous community composition, but not overall diversity, change with changes in land use, but this does not correspond to significant change in Bd-inhibitory function. We found that Bd-inhibition is a functionally redundant trait, but that level of inhibition varies over phylogenetic, spatial, and temporal scales. This research provides further evidence for the importance of continued examination of amphibian microbial communities across environmental gradients, including biotic and abiotic interactions, when considering disease dynamics.

Clinical application of near infrared fiber optic spectroscopy for noninvasive bone assessment.

Approaches for noninvasive bone quality assessment are of great clinical need, particularly in individuals that require close monitoring of disease progression. X-ray measurements are standard approaches to assess bone quality; however, they have several disadvantages. Here, a nonionizing approach for noninvasive assessment of the second metacarpal bone based on near infrared (NIR) spectroscopy was investigated. Transcutaneous bone signal detection was experimentally confirmed with cadaveric hand data, and Monte Carlo modeling further indicated that 50% of the measured signals arise from bone. Spectral data were collected via a NIR fiber optic from the bone of individuals with osteogenesis imperfecta, a disease marked by frequent bone fractures and fragility. Multiple significant correlations were found between spectral parameters related to water, protein and fat, and standard bone quality parameters obtained by X-ray measurements. The results from this preliminary study highlight the potential application of NIR spectroscopy for the noninvasive assessment of bone quality.

Blood pressure in adults with short stature skeletal dysplasias.

Hypertension, compounded by obesity, contributes to cardiovascular disease and mortality. Data describing hypertension prevalence in adults with short stature skeletal dysplasias are lacking, perhaps due to poor fit of typical adult blood pressure cuffs on rhizomelic or contracted upper extremities. Through health screening research, blood pressure was measured in short stature adults attending support group meetings and skeletal dysplasia clinics. Blood pressure was measured with a commercially available, narrower adult cuff on the upper and/or lower segment of the arm. Height, weight, age, gender, diagnosis, exercise, and medications were collected. Subjects were classified as normotensive, prehypertensive, or hypertensive for group analysis; no individual clinical diagnoses were made. In 403 short stature adults, 42% were hypertensive (systolic >140, diastolic >90 OR taking antihypertensive medications). For every BMI unit and 1 kg weight increase in males, there was a 9% and an 8% increase, respectively, in the odds of hypertension versus normotension. In females, the increase was 10% and 6%, respectively. In those with achondroplasia, the most common short stature dysplasia, males (n = 106) had 10% greater odds of hypertension versus normotension for every BMI unit and kilogram increase. In females with achondroplasia (n = 128), the odds of hypertension versus normotension was 8% greater for each BMI unit and 7% for each additional kilogram. These data suggest a high population prevalence of hypertension among short stature adults. Blood pressure must be monitored as part of routine medical care, and measuring at the forearm may be the only viable clinical option in rhizomelic short stature adults with elbow contractures.

Hearing loss in individuals with osteogenesis imperfecta in North America: Results from a multicenter study.

Hearing loss (HL) is an extra-skeletal manifestation of the connective tissue disorder osteogenesis imperfecta (OI). Systematic evaluation of the prevalence and characteristics of HL in COL1A1/COL1A2-related OI will contribute to a better clinical management of individuals with OI. We collected and analyzed pure-tone audiometry data from 312 individuals with OI who were enrolled in the Linked Clinical Research Centers and the Brittle Bone Disorders Consortium. The prevalence, type, and severity of HL in COL1A1/COL1A2-related OI are reported. We show that the prevalence of HL in OI is 28% and increased with age in Type I OI but not in Types III and IV. Individuals with OI Types III and IV are at a higher risk to develop HL in the first decade of life when compared to OI Type I. We also show that the prevalence of SNHL is higher in females with OI compared to males. This study reveals new insights regarding prevalence of HL in OI including a lower general prevalence of HL in COL1A1/COL1A2-related OI than previously reported (28.3 vs. 65%) and high prevalence of SNHL in females. Our data support the need in early routine hearing evaluation in all types of OI that can be adjusted to the severity of the skeletal disease.

Acetabular Protrusio in Patients With Osteogenesis Imperfecta: Risk Factors and Progression.

BACKGROUND: Osteogenesis imperfecta (OI) is a genetic disorder commonly associated with osteopenia, osteoporosis, bone fractures, bone deformities, and other clinical features. A frequent radiologic finding with OI is acetabular protrusio (AP). We hypothesized that AP develops in patients with OI over time. In addition, we hypothesized that AP also develops in patients with OI without radiographic evidence of AP on initial examination. METHODS: Medical records and radiographs of 55 patients (109 hips) diagnosed with OI evaluated at our institution were retrospectively reviewed. Previously established radiographic criteria using the center-edge (CE) angle of Wiberg, position of the acetabulum relative to the iliopectineal line, crossing of the acetabulum across the ilioischial (Kohler) line, and position of the teardrop figure relative to the ilioischial (Kohler) line were utilized to assess AP severity. In addition, pharmacological treatments and patient factors including body mass index (BMI) were recorded. Radiographs of patients with OI that were taken ≥2 years apart were analyzed utilizing AP radiographic criteria to assess for changes. The changes in AP-related measurements were standardized by distance or degree per year. In addition, patient factors were evaluated for associations with AP development. RESULTS: In this series of 109 hips (55 patients), incidence of AP in earliest radiographs was 45% (49/109). Patients with OI type I and III demonstrated the highest incidence of AP (65%). Among the hips that did not meet the criteria for AP in their early radiographs, 24 (40%) were positive for AP by their latest radiograph. In the hips that initially presented with AP, 42% showed increased CE angles on later radiographs. Twenty-six hips (24%) showed either no observable changes or reduced CE angles. Risk factors that were significantly associated with greater odds of developing AP included (1) an age under 12; (2) a BMI>25; (3) presence of AP of the contralateral hip; and (4) female sex. Bisphosphonates, vitamin D, physical therapy, and other drugs related to treatment of OI reduced the risk of developing AP but did not achieve statistical significance. CONCLUSIONS: AP is a common finding in OI patients (54%). Among hips of OI patients that met criteria for AP in early radiographs, 42% (20/48) demonstrated greater CE angles in their latest radiographs. Similar changes were observed in OI patients who did not initially meet criteria for diagnosis for AP. However, CE angle measurements between the 2 groups did not significantly differ (P=0.71). In terms of Kohler line crossing, patients that met criteria for AP in early radiographs had significantly greater change per year than those that did not have AP criteria (P<0.05). The findings suggest AP may develop over time in patients with OI and may be influenced by patient factors such as age, sex, and BMI. In addition, unilateral AP may have a significant impact on the development of AP of the contralateral hip. LEVEL OF EVIDENCE: Level IV-retrospective case series.