Objectives

X-linked hypophosphataemic rickets (XLHR) is a disease of impaired bone mineralization characterized by hypophosphataemia caused by renal phosphate wasting. The main clinical manifestations of the disorder are O-shaped legs, X-shaped legs, delayed growth, and bone pain. XLHR is the most common inheritable form of rickets, with an incidence of 1/20 000 in humans. It accounts for approximately 80% of familial cases of hypophosphataemia and serves as the prototype of defective tubular phosphate (PO4³⁺) transport, due to extra renal defects resulting in unregulated FGF23 activity. XLHR is caused by loss-of-function mutations in the PHEX gene. The aim of this research was to identify the genetic defect responsible for familial hypophosphataemic rickets in a four-generation Chinese Han pedigree and to analyze the function of this mutation.

Introduction Intervertebral disc degeneration may cause chronic low back pain. Disc degeneration is characterized by dysfunctional cells and a decrease in extra-cellular components. Bone marrow derived mononuclear cells are a heterogeneous cell population which contains mesenchymal stem cells. Transplantation of stem cells and progenitor cells may provide a new approach to treat disc degeneration, but it is unclear if transplanted cells can survive and differentiate in the non-vascularized disc.

Methods Bone marrow was collected from syngeneic Sprague-Dawley rats and mononuclear cells were isolated. The cells were labelled with a fluorescence dye (Cell Tracker Orange) and suspended in PBS. 10–20μl of the cell suspension (1–2x10⁵ cells/disc) was transplanted into coccygeal discs in 12 syngeneic rats. For each rat two discs were cell transplanted and one disc served as control. The rats were sacrificed after 0, 7, 14 or 21 days. For each time point the discs from one animal were saved for routine histological staining. The cell transplanted discs of the other animals (n=4 discs per time point) were formalin-fixed, frozen and sectioned together with the control discs. Frozen disc sections were visualized with fluorescence microscopy and the number of transplanted cells assessed. Expression of collagen II, a marker of chondrocytes and chondrocyte-like cells in the disc, was assessed in the transplanted cells using immunofluorescence technique.

Results All cell-suspension injected discs contained transplanted bone-marrow cells. The discs within each time-group demonstrated a large variation in number of detected cells. There was a decrease in detected cells at 7, 14 and 21 days compared to day 0. Transplanted cells expressed collagen II after 21 days but not after 7 and 14 days.

Discussion The results suggest that transplanted bone marrow-derived mononuclear cells can survive and differentiate within the intervertebral disc. Further studies in models of disc degeneration are warranted to investigate the regenerative potential of the disc following cell transplantation.

Introduction and Aims: While clinical variables are considered important risk factors for post-arthroplasty VTE, the role of common genetic thrombophilic factors is less clear. The aims of this study were to determine if common thrombophilic genetic polymorphisms are independent risk factors for VTE post-arthroplasty; and if clinical variables are equally or more important.

Method: A prospective study of consecutive patients undergoing elective total hip or knee arthroplasty at a single institution, involving two surgeons. Patients were interviewed to assess clinical risks. Pre-operative blood samples were taken for Factor V Leiden (FVL), Pro-thrombin G20210A (PTH) and Methylenetetrahydrofolate reductase C677T (MTHFR) testing. All patients received routine enoxaparin prophylaxis and compression stockings. Intermittent pneumatic calf compression was also used by one surgeon. Presence of DVT was assessed using bilateral lower limb duplex ultrasonography (seven ± two days post-operatively) in all patients and performed in a vascular laboratory. Symptoms suggestive of pulmonary embolism were investigated by ventilation/perfusion lung scanning.

Results: A total of 569 patients were recruited with a median age of 67 years (range 20–90). Osteoarthritis was the main surgical indication. The overall incidence of post-operative venous thromboembolism (VTE) was 26%. Of thromboembolic events, 15% VTE were proximal DVT; 84% VTE were distal DVT and only one percent were pulmonary emboli. Prevalence of the thrombophilic genotypes was: 4.6% (heterozygous FVL mutation); 2.1% (heterozygous PTH); and 10.4% (homozygous C677T MTHFR mutation). Using univariate analysis, older age (p < 0.0005), total knee arthroplasty (p < 0.0005), recent surgery (p = 0.002), general anaesthesia (p = 0.013), operation time in minutes (p < 0.0005) and use of blood transfusions (p < 0.0005) were significantly associated with post-operative DVT. None of the thrombophilic genotypes were found to be significantly associated with post-operative DVT, however the frequency of FVL and PTH was highest in patients with proximal DVT and total hip arthroplasty patients with DVT. In multivariate analysis of both genetic and clinical thrombophilic factors, only age (p=0.02) and total knee arthroplasty (p< 0.0005) were found to be significant independent risk factors for post-operative VTE.

Conclusion: We conclude that clinical factors such as age and type of surgery (total knee arthroplasty) are independent risks for post-operative VTE in patients undergoing lower limb arthroplasty. FVL, PTH and MTHFR are not significant risk factors for post-operative VTE and screening for these mutations is not indicated.