Incorporating the patient perspective in the study of rare bone disease: insights from the osteogenesis imperfecta community.

There is limited research which examines health concerns of individuals with osteogenesis imperfecta (OI). Discussion groups with leaders of the adult OI community identified a broad range of medical priorities beyond fractures and brittle bones. Our work underscores the need to include patient-reported outcomes in rare bone disease research. INTRODUCTION: Osteogenesis imperfecta (OI) is a rare genetic disorder affecting collagen protein leading to brittle bones and a number of other medical complications. To date, there is limited research which examines the life-long process of aging with this rare disease, much less the perspective of individuals with OI. METHODS: In order to explore and prioritize health concerns that adults with OI feel have been inadequately addressed in health care and research, investigators held discussions with leaders from the global adult OI community. The meetings were held in August 2017 at the 13th International Conference on OI in Oslo, Norway as part of the preconference seminar "Patient Participation in OI Research". Investigators were part of the Brittle Bone Disease Consortium (BBDC), a multicenter research program devoted to the study of OI, and their focus was on patient-reported outcomes (PRO). RESULTS: Participants noted that while fractures and brittle bones are the most common feature of OI, a number of body systems are under-studied in this disorder. They particularly emphasized breathing, hearing, and the effects of aging as primary concerns that researchers and physicians may not fully understand or address. Other areas included pain, gastrointestinal problems, mental health, nutrition, menopause/pregnancy, and basilar invagination. Participants also emphasized that they must be informed of study results. They underscored that outcome measures incorporated into future drug trials must look beyond fractures and consider the whole patient. CONCLUSIONS: This work will help guide the incorporation of PROs into the next phase of the BBDC Natural History Study of OI and underscores the importance of including PROs in the study of rare diseases.

The American Orthopaedic Association's Own the Bone® database: a national quality improvement project for the treatment of bone health in fragility fracture patients.

The American Orthopaedic Association initiated the Own the Bone (OTB) quality improvement program in 2009. Herein we show that the data collected through this program is similar to that collected in other large studies. Thus, the OTB registry functions as an externally valid cohort for studying fragility fracture patients. INTRODUCTION: The American Orthopedic Association initiated the Own the Bone (OTB) quality improvement program in 2009 to improve secondary prevention of fragility fractures. In this study, we present a summary of the data collected by the OTB program and compare it to data from other large fragility fracture registries with an aim to externally validate the OTB registry. METHODS: The OTB registry contained 35,038 unique cases of fragility fracture as of September, 2016. We report the demographics, presenting fracture characteristics, past fracture history, and bone mineral density (BMD) data and compare these to data from large fragility fracture studies across the world. RESULTS: Seventy-three percent of the patients in the OTB registry were female, Caucasian, and post-menopausal. In 54.4% of cases, patients had a hip fracture; spine fractures were the second most common fracture type occurring in 11.1% of patients. Thirty-four percent of the patients had a past history of fragility fracture, and the most common sites were the spine and hip. The average femoral neck T-score was - 2.06. When compared to other studies, the OTB database showed similar findings with regard to patient age, gender, race, BMI, BMD profile, prior fracture history, and family history of fragility fractures. CONCLUSION: OTB is the first and largest multi-center voluntary fragility fracture registry in the USA. The data collected through the OTB program is comparable to that collected in international studies. Thus, the OTB registry functions as an externally valid cohort for further studies assessing the clinical characteristics, interventions, and outcomes achieved in patients who present with a fragility fracture in the USA.

Cutaneous skeletal hypophosphatemia syndrome: clinical spectrum, natural history, and treatment.

Cutaneous skeletal hypophosphatemia syndrome (CSHS), caused by somatic RAS mutations, features excess fibroblast growth factor-23 (FGF23) and skeletal dysplasia. Records from 56 individuals were reviewed and demonstrated fractures, scoliosis, and non-congenital hypophosphatemia that in some cases were resolved. Phosphate and calcitriol, but not skin lesion removal, were effective at controlling hypophosphatemia. No skeletal malignancies were found. PURPOSE: CSHS is a disorder defined by the association of epidermal and/or melanocytic nevi, a mosaic skeletal dysplasia, and an FGF23-mediated hypophosphatemia. To date, somatic RAS mutations have been identified in all patients whose affected tissue has undergone DNA sequencing. However, the clinical spectrum and treatment are poorly defined in CSHS. The purpose of this study is to determine the spectrum of the phenotype, natural history of the disease, and response to treatment of hypophosphatemia. METHODS: Five CSHS subjects underwent prospective data collection at clinical research centers. A review of the literature identified 45 reports that included a total of 51 additional patients, in whom the findings were compatible with CSHS. Data on nevi subtypes, bone histology, mineral and skeletal disorders, abnormalities in other tissues, and response to treatment of hypophosphatemia were analyzed. RESULTS: Fractures, limb deformities, and scoliosis affected most CSHS subjects. Hypophosphatemia was not present at birth. Histology revealed severe osteomalacia but no other abnormalities. Skeletal dysplasia was reported in all anatomical compartments, though less frequently in the spine; there was no clear correlation between the location of nevi and the skeletal lesions. Phosphate and calcitriol supplementation was the most effective therapy for rickets. Convincing data that nevi removal improved blood phosphate levels was lacking. An age-dependent improvement in mineral abnormalities was observed. A spectrum of extra-osseous/extra-cutaneous manifestations that included both benign and malignant neoplasms was present in many subjects, though osteosarcoma remains unreported. CONCLUSION: An understanding of the spectrum, natural history, and efficacy of treatment of hypophosphatemia in CSHS may improve the care of these patients.

Dislocation of hip in myelomeningocele. The McKay hip stabilization.

We reviewed the clinical and radiographic results of varus osteotomy of the proximal aspect of the femur and transfer of the adductor and external oblique muscles (the McKay procedure) in thirty-four children (sixty-six hips) who had an unstable hip secondary to a myelomeningocele at the middle or caudad lumbar level. the average age at the time of the operation was twenty months (range, seven to forty-two months). The average duration of follow-up was 10.9 years (range, 0.7 to 20.0 years). An open reduction was performed in ten hips. None of the children had had any previous operative treatment. The index operation helped to maintain the stability of thirty-seven of the fifty-one hips twenty-six children who remained neurologically stable: seventeen of nineteen hips that were at risk, two of three hips with acetabular dysplasia, fifteen of sixteen subluxated hips, one of three dislocated hips that had been previously reduced with a Pavlik harness, one of two dislocatable hips, and one of seven previously untreated dislocated hips. The index operation was not successful for one dislocated hip that had been treated with closed reduction and application of a spica cast. The operation was a success for eight of the fifteen hips in eight children who had a progressive loss of neurological function: three of five hips that were at risk, one hip with acetabular dysplasia, two of four subluxated hips, one of two that had been previously reduced with a Pavlik harness, and one dislocatable hip. Two dislocated hips redislocated. Initially the index operation was performed on all children who had a myelomeningocele at the third or fourth lumbar level. Recent data have shown that the hips in these children are not all at risk, and we now perform the operation only if there is documented instability of the hip.

Women and the orthopaedic surgeon. Changing the relationship.

Women are disproportionately disabled by musculoskeletal conditions. For biologic and lifestyle reasons, musculoskeletal health is one of the areas of medicine in which the differences between men and women are most marked. Thus, an approach tailored to women, not just an approach based on what has worked for men, often is needed. How orthopaedists treat women will become an even more pressing issue in the years ahead. Demographic trends predict that the majority of senior citizens will be women in whom chronic conditions frequently involve a musculoskeletal problem. Even at earlier ages, women will present more frequently with musculoskeletal conditions because they participate in a broader range of sports and careers. The current study presents a lengthy list of action items that the orthopaedic surgeon should consider as he or she approaches the treatment of women. Many of these items involve anticipating musculoskeletal problems, and convincing patients to take appropriate preventive steps. Because so many patients are treated by physicians who are not orthopaedists for their musculoskeletal problems, a successful preventive approach presents orthopaedists with the opportunity to win the confidence and respect of a new generation of patients.

Osteogenesis imperfecta.

In the past 20 years, tremendous strides have been made in our understanding of the biochemical and genetic abnormalities associated with osteogenesis imperfecta (OI). Prenatal diagnostic techniques have allowed early detection of this disorder, particularly in families in which the actual molecular defect is already known. Although medical and surgical management of patients with OI continue to improve, the proper management of such problems as basilar impression still need to be determined. Progress in the treatment of OI at a molecular level is encouraging.

Ensuring the success of women in academic orthopaedics.

In spring of 1995, the Academic Orthopaedic Society convened a panel of 21 female academic orthopaedists and 24 senior members of the society to discuss the challenges facing female orthopaedic residents and women in academic orthopaedics. Participants began by reviewing results of a 200 item mail survey of fulltime and parttime female academic orthopaedic surgeons. The survey had been conducted in early 1995. Using the Delphi technique, the panelists identified challenges facing women and ranked them in priority order. Although the challenges identified by survey respondents and panelists were similar, the priority assigned to them varied. Panel and survey findings pointed to a need for action in six areas: increasing mentoring; overcoming gender bias; reducing women's social and professional isolation; increasing attention to promotion and salary equity; providing greater accommodation for family responsibilities; and expanding recruitment efforts. This paper suggests actions that department chairpersons and the Academic Orthopaedic Society may take to attract more women to academic orthopaedics. Because many of the issues emerging from the survey and panel were not gender specific, implementation of the recommendations may benefit male and female orthopaedic residents and academic surgeons in general.

Percutaneous intramedullary fixation of long bone deformity in severe osteogenesis imperfecta.

Reported here are seven patients who had severe osteogenesis imperfecta, and who were extremely fragile, with three having cardiac disease. Their age ranged between 8 and 35 months. All seven patients had unbraceable deformities. Twenty five long bones, including 14 tibiae, 10 femora, and 1 ulna underwent percutaneous intramedullary fixation. Four patients had all four lower extremity long bones operated on simultaneously. Followup was 2 to 11 years. There were no neurologic or vascular complications, compartment syndromes, growth plate problems, or transfusion requirements. All bones healed. One patient had migration of a femoral pin into the knee joint. After bracing, all patients were able to sit; five were able to stand and eventually walk. All living patients were able to be sustained until successful definitive long bone fixation could be accomplished, approximately 2 years or longer after this initial procedure. With this safe, reproducible method, early stable fixation can be provided to patients too young and/or too sick for definitive or extensive open surgery. Future treatment regimens are not compromised.

Latex allergy in spina bifida patients: prevalence and surgical implications.

We interviewed 93 consecutive children with spina bifida who were scheduled for operation to document (a) the prevalence of latex sensitivity, (b) predictors of anaphylactic reaction, and (c) the risk of type I hypersensitivity reaction perioperatively. Of these patients, 9.7% were clinically allergic. Radioallergosorbent testing (RAST) was 89% sensitive. All patients with known latex allergy were premedicated, and rigorous efforts were made to avoid latex exposure. No intraoperative anaphylactic reactions were noted. One postoperative reaction occurred in a history-positive, RAST-negative patient. We conclude that operation can be performed safely in patients with latex allergy.

When does mass screening for open neural tube defects in low-risk pregnancies result in cost savings?

Using a decision analysis model, we estimated the savings that might be derived from a mass prenatal screening program aimed at detecting open neural tube defects (NTDs) in low-risk pregnancies. Our baseline analysis showed that screening v. no screening could be expected to save approximately $8 per pregnancy given a cost of $7.50 for the maternal serum alpha-feto-protein (MSAFP) test and a cost of $42,507 for hospital and rehabilitation services for the first 10 years of life for a child with spina bifida. When a more liberal estimate of the costs of caring for such a child was used, the savings with the screening program were more substantial. We performed extensive sensitivity analyses, which showed that the savings were somewhat sensitive to the cost of the MSAFP test and highly sensitive to the specificity (but not the sensitivity) of the test. A screening program for NTDs in low-risk pregnancies may result in substantial savings in direct health care costs if the screening protocol is followed rigorously and efficiently.

Proposed curriculum model for resident education in pediatric orthopaedic surgery.

A curriculum developed for pediatric orthopaedic residency training is described. The curriculum is practice based, emphasizing those components thought to be necessary for orthopaedic practice. Highly technical or esoteric topics are deemphasized, because they are not relevant to practice capabilities at the end of residency training. The curriculum is designed to serve as a guide for educational direction in pediatric orthopaedic residency training, and not as a description of competency. Resource materials are being developed to provide the educator with relevant clinical material, objectives, and bibliography. The advantages of a practice based curriculum warrant further development of this model for other orthopaedic subspecialties.

Ligamentous instability of the knee in children sustaining fractures of the femur: a prospective study with knee examination under anesthesia.

Fifty-five children with 55 fractures of the femur were prospectively studied for the presence of ligamentous instability of the knee within 3 weeks from the time of injury. Two patients (4%) demonstrated instability on examination under anesthesia. A 9-year, 4-month-old boy sustained a second-degree injury to the lateral collateral ligament that healed after hip spica cast treatment. The other patient, a 12-year, 8-month-old boy, sustained an avulsion fracture of the posterior cruciate ligament from the tibial insertion with > 1 cm posterior displacement of the tibia on the posterior drawer test. After placement of an intramedullary rod, the avulsion fracture was treated with open reduction and internal fixation. Although the incidence of ligamentous instability of the knee in this study is less than that reported for adults with femur fractures, children should nevertheless have a thorough knee examination for ligamentous stability as well as radiographic evaluation of the knee.