Lower limb bone geometry in adult individuals with X-linked hypophosphatemia: an observational study

Summary: We assessed lower-limb geometry in adults with X-linked hypophosphatemia (XLH) and controls. We found large differences in multiple measures including femoral and tibial torsion, bowing and cross-sectional area and acetabular version and coverage which may contribute to clinical problems such as osteoarthritis, fractures and altered gait common in XLH. Purpose: Individuals with X-linked hypophosphatemia (XLH) are at risk of lower-limb deformities and early onset of osteoarthritis. These two factors may be linked, as altered biomechanics is a risk factor for osteoarthritis. This exploratory evaluation aims at providing clues and concepts for this association to facilitate future larger-scale and longitudinal studies on that aspect. Methods: For this observational study, 13 patients with XLH, aged 18–65 years (6 female), were compared with sex-, age- and weight-matched healthy individuals at a single German research centre. Femoral and hip joint geometry, including femoral and tibial torsion and femoral and tibial shaft bowing, bone cross-sectional area (CSA) and acetabular version and coverage were measured from magnetic resonance imaging (MRI) scans. Results: Total femoral torsion was 29° lower in individuals with XLH than in controls (p < 0.001), mainly resulting from lower intertrochanteric torsion (ITT) (p < 0.001). Femoral lateral and frontal bowing, tibial frontal bowing, mechanical axis, femoral mechanical–anatomical angle, acetabular version and acetabular coverage were all greater and tibial torsion lower in individuals with XLH as compared to controls (all p < 0.05). Greater femoral total and marrow cavity CSA, greater tibial marrow cavity CSA and lower cortical CSA were observed in XLH (all p < 0.05). Discussion: We observed large differences in clinically relevant measures of tibia and particularly femur bone geometry in individuals with XLH compared to controls. These differences may plausibly contribute to clinical manifestations of XLH such as early-onset osteoarthritis, pseudofractures and altered gait and therefore should be considered when planning corrective surgeries

Patient-reported experience of clinical care of osteogenesis imperfecta (OI) during the COVID-19 pandemic

Background: Research on the effects of the COVID-19 pandemic on people with rare diseases is limited. Few studies compare healthcare throughout the progression of the ongoing pandemic. Aims: To assess the impact of the pandemic on individuals with osteogenesis imperfecta across two consecutive years, understand what challenges were encountered, and analyse the experience of remote consultation. Methods: An initial survey was distributed following the first lockdown in August 2020, and a second survey in April 2021. The surveys explored four themes- effects on therapy, alternatives to consultation, effect on mental health, and perceived risks of COVID-19. Results: In the 2020 survey, of the 110 respondents, 69 (63%) had at least one appointment delayed due to the lockdown, compared with 89 of the 124 respondents (72%) in 2021. Of the 110 respondents in 2020, 57 (52%) had a remote consultation, increasing to 92 of 124 (74%) in the follow-up survey. In the 2020 survey 63 of 91 respondents (69%) expressed anxiety due to lockdown, compared with 76 of 124 (61%) in 2021. The percentage of total respondents expressing a preference for remote consultation was 48% in 2020, increasing to 71% in 2021. Conclusions: The pandemic has had widespread effects on the mental and physical health of those with OI. These effects, alongside appointment delays, have increased as the pandemic progresses. Encouragingly, the increasing preference for remote consultation may indicate that this could be a viable long-lasting alternative to face-to-face appointments, especially for patients who previously traveled vast distances for specialist care

FDG-PET underscores the key role of the thalamus in frontotemporal lobar degeneration caused by C9ORF72 mutations

C9ORF72 mutations are the most common cause of familial frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). MRI studies have investigated structural changes in C9ORF72-associated FTLD (C9FTLD) and provided first insights about a prominent involvement of the thalamus and the cerebellum. Our multicenter, F-18-fluorodeoxyglucose positron-emission tomography study of 22 mutation carriers with FTLD, 22 matched non-carriers with FTLD, and 23 cognitively healthy controls provided valuable insights into functional changes in C9FTLD: compared to non-carriers, mutation carriers showed a significant reduction of glucose metabolism in both thalami, underscoring the key role of the thalamus in C9FTLD. Thalamic metabolism did not correlate with disease severity, duration of disease, or the presence of psychotic symptoms. Against our expectations we could not demonstrate a cerebellar hypometabolism in carriers or non-carriers. Future imaging and neuropathological studies in large patient cohorts are required to further elucidate the central role of the thalamus in C9FTLD

Analyses of muscular mass and function: the impact on bone mineral density and peak muscle mass

Bone density and bone mass are commonly regarded as the essential parameters to describe fracture risk in osteology. Because fractures primarily depend on bone strength and secondarily on bone mass and density, bone strength should be the main parameter to describe fracture risk. The quantitative description of bone strength has the prerequisite that bone geometry is assessed despite bone density. Thus, volumetric osteodensitometric methods should be preferred, which enable the physician to evaluate parameters primarily associated with bone modeling or remodeling. Modeling describes the adaptation of bone geometry to applied muscular forces in contrast to remodeling representing bone turnover. The adaptation of bone geometry to muscle forces led to the term functional muscle-bone unit, which enables the physician to differentiate between primary and secondary bone diseases. Primary bone diseases are characterized by a defective adaptation of bone to muscle forces in contrast to secondary bone diseases, which are primary diseases of the neuromuscular system. Because muscle forces are essential in the feedback loop of bone adaptation to forces (mechanostat), the assessment of muscle function has become an essential part of osteologic diagnostics in pediatrics. Dynamometric and mechanographic methods have been introduced to properly characterize kinetic aspects of muscle function in children and adolescents. Therefore, emphasis should be put on the assessment of muscle function despite the evaluation of osteodensitometric parameters in pediatric osteology

Osteogenesis imperfecta: pathophysiology and treatment

Osteogenesis imperfecta is a rare hereditary disease mostly caused by mutations impairing collagen synthesis and modification. Recently recessive forms have been described influencing differentiation and activity of osteoblasts and osteoclasts. Most prominent signs are fractures due to low traumata and deformities of long bones and vertebrae. Additional patients can be affected by dwarfism, scoliosis Dentinogenesis imperfecta, deafness and a blueish discoloration of the sclera. During childhood state of the art medical treatment are i.v. bisphosphonates to increase bone mass and to reduce fracture rate. Surgical interventions are needed to treat fractures, to correct deformities and should always be accompanied by physiotherapeutic and rehabilitative interventions

Pathophysiology and therapeutic options in osteogenesis imperfecta

Osteogenesis imperfecta (OI) is the most common hereditary disease causing an increased bone fragility. The wide variability of the phenotype can not be explained by the genotype. Most forms are caused by mutations in genes influencing synthesis and posttranslational modification of collagen. Most patients are affected by mutations in the genes COL1A1/A2. The increased knowledge about underlying genetic alteration and pathophysiology in some rare recessive forms has led to new therapeutic strategies. OI VI is caused by mutations in SERPINF1 leading to an increased activity of osteoclasts via the OPG/RANKL-pathway. In these patients a medical treatment with denosumab has been proven to be more effective as antiresorptive treatment compared to the former therapy with bisphosphonates. In patients affected by mutations in WNT1 an osteoanabolic treatment might be more suitable than an antiresorptive therapy. Pharmacological treatment has to be included in an interdisciplinary therapeutic concept in combination with physiotherapy and surgical treatment

Hip Pain in Children

Background: Atraumatic hip pain in children is one of the most common symptoms with which pediatricians, orthopedists, and general practitioners are confronted, with an incidence of 148 cases per 100 000 persons per year. Methods: This article is based on publications up to April 2019 that were retrieved by a selective search in the PubMed database, including case reports and reviews. Results: Infants with fever often have purulent coxitis, which can be diagnosed by blood tests and ultrasonography. Toddlers and older children may suffer from painful restriction of motion of the hip joint, associated with limping (antalgic gait) or even the inability to walk. The main elements of the differential diagnosis in children aged 2-10 are coxitis fugax and idiopathic necrosis of the femoral head (Perthes disease). In children aged 10 and up, and in adolescents, slipped capital femoral epiphysis (SCFE) is typical. Bone tumors and rheumatic diseases must always be considered as well. The initial diagnostic steps on presentation of a child with restricted hip movement should be plain x-rays and joint ultrasonography for the detection of an effusion. Suspicion of a tumor is the main indication for tomographic imaging (computed tomography or magnetic resonance imaging). Conclusion: The underlying cause of hip pain in children should be diagnosed early to avoid adverse sequelae