Impaired WNT signaling and the spine-Heterozygous WNT1 mutation causes severe age-related spinal pathology

Background: WNT signaling plays a major role in bone and cartilage metabolism. Impaired WNT/beta-catenin signaling leads to early-onset osteoporosis, but specific features in bone and other tissues remain inadequately characterized. We have identified two large Finnish families with early-onset osteoporosis due to a heterozygous WNT1 mutation c.652T>G, p.C218G. This study evaluated the impact of impaired WNT/beta-catenin signaling on spinal structures. Methods: Altogether 18 WNT1 mutation-positive (age range 11-76 years, median 49 years) and 14 mutation negative subjects (10-77 years, median 43 years) underwent magnetic resonance imaging (MRI) of the spine. The images were reviewed for spinal alignment, vertebral compression fractures, intervertebral disc changes and possible endplate deterioration. The findings were correlated with clinical data. Results: Vertebral compression fractures were present in 78% (7/9) of those aged over 50 years but were not seen in younger mutation-positive subjects. All those with fractures had several severely compressed vertebrae. Altogether spinal compression fractures were present in 39% of those with a WNT1 mutation. Only 14% (2/14) mutation -negative subjects had one mild compressed vertebra each. The mutation-positive subjects had a higher mean spinal deformity index (4.0 +/- 7.3 vs 0.0 +/- 0.4) and more often increased thoracic kyphosis (Z-score > + 2.0 in 33% vs 0%). Further, they had more often Schmorl nodes (61% vs 36%), already in adolescence, and their intervertebral discs were enlarged. Conclusion: Compromised WNT signaling introduces severe and progressive changes to the spinal structures. Schmorl nodes are prevalent even at an early age and increased thoracic kyphosis and compression fractures become evident after the age of 50 years. Therapies targeting the WNT pathway may be an effective way to prevent spinal pathology not only in those harboring a mutation but also in the general population with similar pathology. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

Functional results of total-knee arthroplasty versus medial unicompartmental arthroplasty:two-year results of a randomised, assessor-blinded multicentre trial

Abstract Objective:The primary objective of the trial was to assess the clinical effectiveness of medial unicompartmental knee arthroplasty versus total knee arthroplasty in patients with isolated medial osteoarthritis of the knee. Design: Prospective, randomised, 2 years, assessor-blind, multicentre, superiority trial. Setting: The patients were enrolled between December 2015 and May 2018 from the outpatient clinics of three public high-volume arthroplasty hospitals (Finland). Participants: We recruited 143 patients with symptomatic-isolated medial osteoarthritis of the knee needing an arthroplasty procedure. All the patients were suitable for both unicompartmental and total knee arthroplasties. Population was selected as the end-stage-isolated medial osteoarthritis. Interventions: All patients, randomized 1:1, received a medial unicompartmental arthroplasty or a total knee arthroplasty through a similar midline skin incision. Patients were blinded to the type of arthroplasty for the whole 2 years of follow-up. Main outcome measures: Primary outcome measure was between-group differences in the Oxford Knee Score (OKS) and secondary outcome Knee injury and Osteoarthritis Score (KOOS) at 2 years postoperatively. The changes within and between the groups were analysed with analysis of variance for repeated measurements. Results: The primary outcome was comparable for medial unicompartmental arthroplasty and total knee arthroplasty at 2 years. The mean difference in the OKS between the groups was 1.6 points (95% CI −0.7 to 3.9). In the KOOS subscales, the mean difference between the groups was 0.1 points (95% CI −4.8 to 5.0) for pain, 7.8 points (95% CI 1.5 to 14.0) for symptoms, 4.3 points (95% CI −0.6 to 9.2) for function in daily living, 4.3 points (95% CI −3.0 to 11.6) for function in sports, and 2.1 points (95% CI −4.8 to 9.1) for knee-related quality of life. Conclusions: The recovery after unicompartmental knee arthroplasty was faster compared with total knee arthroplasty, but unicompartmental arthroplasty did not provide a better patient-reported outcome at 2 years. Trial registration number: NCT02481427