Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Scorcelletti M

PROVIDER: S-EPMC9187561 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Scorcelletti Matteo M Kara Serhan S Zange Jochen J Jordan Jens J Semler Oliver O Schönau Eckhard E Rittweger Jörn J Ireland Alex A Seefried Lothar L

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 20220418 7

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.<h4>Purpose</h4>Individuals with X-linked hypophosphatemia (XLH) are at risk of lower-limb deformities and early onset of osteoarthritis. These tw ...[more]

PMID: 35435480

Similar Datasets

Project description:BackgroundGait deviations, lower limb pain and joint stiffness represent key symptoms in patients with X-linked hypophosphatemia (XLH, OMIM 307800), a rare disorder of mineral homeostasis. While the pathomechanism for rickets is well understood, the direct role of PHEX (Phosphate-regulating neutral endopeptidase) deficiency in non-rachitic features including complex deformities, skull and dental affections remains unclear. FGF23-inhibiting antibody treatment can normalize serum phosphate levels and to improve rickets in XLH patients. However, linear growth remains impaired and effects on lower limb deformity and gait are insufficiently studied.AimsTo characterize and evaluate the course of lower limb deformity in a case series of pediatric XLH patients receiving Burosumab therapy.MethodsComparative assessment of planar radiographs, gait analysis, biochemical and clinical features of pediatric patients before and ≥12 months after initiation of FGF23-inhibiting was performed prospectively. Lower limb maltorsion was quantified by torsional MRI and gait analysis. Standardized deformity analysis of lower limb anteroposterior radiographs was conducted.ResultsSeven patients (age 9.0 +/-3.6 years) were eligible for this study. All patients received conventional treatment before onset of antibody treatment. Maltorsion of the femur was observed in 8/14 legs using torsional MRI (mean antetorsion 8.79°). Maltorsion of the tibia was observed in 9/14 legs (mean external torsion 2.8°). Gait analysis confirmed MRI findings with femoral external malrotation prior to and one year after onset of Burosumab therapy. Internal foot progression (intoeing gait) remained pathological in all cases (mean 2.2°). Knee rotation was pathologically internal 10/14 legs. Mean mechanical axis deviation (MAD) of 16.1mm prior to Burosumab changed in average by 3.9mm. Three children underwent guided growth procedures within the observation period. Mild postprocedural rebound of frontal axis deviation was observed under Burosumab treatment in one patient.ConclusionsThis is the first study to investigate lower limb deformity parameters quantitatively in children with XLH receiving Burosumab. One year of Burosumab therapy was associated with persistent maltorsion and frontal axis deviation (varus/valgus) despite improved rickets in this small, prospective uncontrolled study.

Project description:IntroductionOnabotulinumtoxinA treatment for spasticity varies according to numerous factors and is individualized to meet treatment goals.ObjectiveTo explore real-world onabotulinumtoxinA utilization and effectiveness in patients with lower limb spasticity from the Adult Spasticity International Registry (ASPIRE) study.DesignTwo-year, multicenter, prospective, observational registry (NCT01930786).SettingFifty-four international clinical sites.PatientsAdults (naïve or non-naïve to botulinum toxin[s] treatment for spasticity, across multiple etiologies) with lower limb spasticity related to upper motor neuron syndrome.InterventionsOnabotulinumtoxinA administered at the clinician's discretion.Main outcome measuresOnabotulinumtoxinA treatment utilization, clinician- and patient-reported satisfaction.ResultsIn ASPIRE, 530 patients received ≥1 onabotulinumtoxinA treatment for lower limb spasticity (mean age, 52 years; stroke, 49.4%; multiple sclerosis, 20.4%). Equinovarus foot was treated most often (80.9% of patients), followed by flexed knee (26.0%), stiff extended knee (22.5%), and flexed toes (22.3%). OnabotulinumtoxinA doses ranged between 10 and 1100 U across all presentations. Electromyography (EMG) was most commonly used for injection localization (≥41.1% of treatment sessions). Despite low patient response on the satisfaction questionnaire, clinicians (94.6% of treatment sessions) and patients (84.5%) reported satisfaction/extreme satisfaction that treatment helped manage spasticity, and clinicians (98.3%) and patients (91.6%) would probably/definitely continue onabotulinumtoxinA treatment. These data should be interpreted with care. Twenty-one adverse events (AEs) in 18 patients (3.4%) were considered treatment-related. Sixty-seven patients (12.6%) reported 138 serious AEs; 3 serious AEs in two patients (0.4%) were considered treatment-related. No new safety signals were identified.ConclusionsASPIRE provides long-term observational data on the treatment of lower limb spasticity with onabotulinumtoxinA. Real-world data from this primary analysis can help to guide the clinical use of onabotulinumtoxinA to improve spasticity management.

Project description:X-linked hypophosphatemia (XLH) is the most common form of genetic rickets. Mainly diagnosed during childhood because of growth retardation and deformities of the lower limbs, the disease affects adults with early enthesopathies and joint structural damage that significantly alter patient quality of life. The conventional treatment, based on phosphorus supplementation and active vitamin D analogs, is commonly administered from early childhood to the end of growth; unfortunately, it does not allow complete recovery from skeletal damage. Despite adequate treatment during childhood, bone and joint complications occur in adults and become a dominant feature in the natural history of the disease. Our previous data showed that the Hyp mouse is a relevant model of XLH for studying early enthesophytes and joint structural damage. Here, we studied the effect of conventional treatment on the development of bone and joint alterations in this mouse model during growth and young adulthood. Mice were supplemented with oral phosphorus and calcitriol injections, following two timelines: (i) from weaning to 3 months of age and (ii) from 2 to 3 months to evaluate the effects of treatment on the development of early enthesophytes and joint alterations, and on changes in bone and joint deformities already present, respectively. We showed that early conventional treatment improved bone microarchitecture, and partially prevented bone and joint complications, but with no noticeable improvement in enthesophytes. In contrast, later administration had limited efficacy in ameliorating bone and joint alterations. Despite the improvement in bone microarchitecture, the conventional treatment, early or late, had no effect on osteoid accumulation. Our data underline the usefulness of the Hyp murine model for preclinical studies on skeletal and extraskeletal lesions. Although the early conventional treatment is important for the improvement of bone microarchitecture, the persistence of osteomalacia implies seeking new therapeutic strategies, in particular anti-FGF23 approach, in order to optimize the treatment of XLH.

Project description:AbstractLower limb amputation (LLA) is still a health issue requiring rehabilitation and long-term care even in industrial societies. Several studies on subjects with LLA have been focused on the efficacy of rehabilitation and factors influencing the use of prosthesis. However, literature data on the recovery of ability to walk outdoors, and thus to participate in social life in this population is limited.To investigate potential correlations between socio-demographic and clinical factors, and the use of the prosthesis for indoor and/or outdoor walking referred to as community ambulation (CA) in subjects with LLA.An observational cohort study on 687 LLA subjects was conducted. Socio-demographic and clinical characteristics of 302 subjects who received similar rehabilitative treatment with respect to the standard protocol were collected by a telephone survey with a structured questionnaire. The CA recovery, in terms of patient's autonomy and participation, assessed by Walking Handicap Scale, was considered as the main outcome.The univariate analysis demonstrated statistical significant positive correlation between CA and gender (χ2 = 3.901, P = .048); amputation level (χ2 = 24.657, P < .001); pre-LLA (χ2 = 6.338, P = .012) and current work activity (χ2 = 25.192, P < .001); prosthesis use (χ2 = 187.037, P < .01); and time from LLA (r = 0.183, P < .001); increasing age was negatively correlated with the outcome (r = -0.329, P < .001), while pain intensity was not significant. Being male (75.4%); trans-tibial (TT) amputation level (9.79%); working before (3.81%) and after LLA (7.68%); and the prosthesis use (24.63%) increased the probability of CA recovery. Multivariate binary logistic regression analysis confirmed that the prosthesis use (P < .001) and TT amputation level (P = .042) are predictors of a positive outcome (Walking Handicap Scale 4-6).These findings highlight the importance of the use of prosthesis in people with LLA for the restoration of a good capacity of participation (CA), especially in subjects with TT amputation level. The identification of predictive factors may help tailor-made rehabilitation approaches addressing an earlier reintegration to social life.

Dataset Information

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

Purpose

Methods

Results

Discussion

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets