Per Kjærsgaard-Andersen

Thromboprophylaxis only during hospitalisation in fast-track hip and knee arthroplasty, a prospective cohort study

Objectives International guidelines recommend thrombosis prophylaxis after total hip arthroplasty (THA) and total knee arthroplasty (TKA) for up to 35u2005days. However, previous studies often have hospital stays (length of stay; LOS) of 8–12u2005days and not considering early mobilisation, which may reduce incidence of venous thromboembolic events (VTE). We investigated the incidence of any symptomatic thromboembolic events (TEEs) with only in-hospital prophylaxis if LOS ≤5u2005days after fast-track THA and TKA. Design A prospective descriptive multicentre cohort study in fast-track THA and TKA from February 2010 to December 2011, with complete 90-day follow-up through the Danish National Patient Registry and patient files. Setting 6 Danish high-volume centres with a similar standardised fast-track setup, including spinal anaesthesia, opioid-sparing analgesia, early mobilisation, functional discharge criteria and discharge to own home. Participants 4924 consecutive unselected unilateral primary THA and TKAs in patients ≥18u2005years with no preoperative use of continuous ‘potent’ anticoagulative therapy (vitamin K antagonists). Exposure Prophylaxis with low-molecular-weight heparin or factor Xa-inhibitors only during hospitalisation when LOS ≤5u2005days. Outcomes Incidence of symptomatic TEE-related, VTE-related and VTE-related mortality ≤90u2005days postoperatively. Results LOS ≤5u2005days and thromboprophylaxis only during hospitalisation occurred in 4659 procedures (94.6% of total). Median LOS and prophylaxis duration was 2u2005days (IQR 2–3) with 0.84% (95% CI 0.62% to 1.15%) TEE and 0.41% (0.26% to 0.64%) VTE during 90-day follow-up. VTE consisted of five pulmonary embolisms (0.11% (0.05% to 0.25%)) and 14 deep venous thrombosis (0.30% (0.18% to 0.50%)). There were four (0.09% (0.04% to 0.23%)) surgery-related deaths, of which 1 (0.02% (0.00% to 0.12%)) was due to pulmonary embolism, and 6 (0.13% (0.06% to 0.28%)) deaths of unknown causes after discharge. Conclusions The low incidence of TEE and VTE suggests that in-hospital prophylaxis only, is safe in fast-track THA and TKA patients with LOS of ≤5u2005days. Guidelines on thromboprophylaxis may need reconsideration in fast-track elective surgery. Trial Registration ClinicalTrials.gov: NCT01557725

Understanding Coupling between Bone Resorption and Formation: Are Reversal Cells the Missing Link?

Bone remodeling requires bone resorption by osteoclasts, bone formation by osteoblasts, and a poorly investigated reversal phase coupling resorption to formation. Likely players of the reversal phase are the cells recruited into the lacunae vacated by the osteoclasts and presumably preparing these lacunae for bone formation. These cells, called herein reversal cells, cover >80% of the eroded surfaces, but their nature is not identified, and it is not known whether malfunction of these cells may contribute to bone loss in diseases such as postmenopausal osteoporosis. Herein, we combined histomorphometry and IHC on human iliac biopsy specimens, and showed that reversal cells are immunoreactive for factors typically expressed by osteoblasts, but not for monocytic markers. Furthermore, a subpopulation of reversal cells showed several distinctive characteristics suggestive of an arrested physiological status. Their prevalence correlated with decreased trabecular bone volume and osteoid and osteoblast surfaces in postmenopausal osteoporosis. They were, however, virtually absent in primary hyperparathyroidism, in which the transition between bone resorption and formation occurs optimally. Collectively, our observations suggest that arrested reversal cells reflect aborted remodeling cycles that did not progress to the bone formation step. We, therefore, propose that bone loss in postmenopausal osteoporosis does not only result from a failure of the bone formation step, as commonly believed, but also from a failure at the reversal step.

The distribution pattern of critically short telomeres in human osteoarthritic knees

IntroductionTelomere shortening is associated with a number of common age-related diseases. A role of telomere shortening in osteoarthritis (OA) has been suggested, mainly based on the assessment of mean telomere length in ex vivo expanded chondrocytes. We addressed this role directly in vivo by using a newly developed assay, which measures specifically the load of ultra-short single telomeres (below 1,500 base pairs), that is, the telomere subpopulation believed to promote cellular senescence.MethodsSamples were obtained from human OA knees at two distances from the central lesion site. Each sample was split into three: one was used for quantification of ultra-short single telomeres through the Universal single telomere length assay (STELA), one for histological Mankin grading of OA, and one for mean telomere length measurement through quantitative fluorescence in situ hybridization (Q-FISH) as well as for assessment of senescence through quantification of senescence-associated heterochromatin foci (SAHF).ResultsThe load of ultra-short telomeres as well as mean telomere length was significantly associated with proximity to lesions, OA severity, and senescence level. The degree of significance was higher when assessed through load of ultra-short telomeres per cell compared with mean telomere length.ConclusionsThese in vivo data, especially the quantification of ultra-short telomeres, stress a role of telomere shortening in human OA.

Does collagen trigger the recruitment of osteoblasts into vacated bone resorption lacunae during bone remodeling

Osteoblast recruitment during bone remodeling is obligatory to re-construct the bone resorbed by the osteoclast. This recruitment is believed to be triggered by osteoclast products and is therefore likely to start early during the remodeling cycle. Several osteoclast products with osteoblast recruitment potential are already known. Here we draw the attention on the osteoblast recruitment potential of the collagen that is freshly demineralized by the osteoclast. Our evidence is based on observations on adult human cancellous bone, combined with in vitro assays. First, freshly eroded surfaces where osteoblasts have to be recruited show the presence of non-degraded demineralized collagen and close cell-collagen interactions, as revealed by electron microscopy, while surface-bound collagen strongly attracts osteoblast lineage cells in a transmembrane migration assay. Compared with other extracellular matrix molecules, collagens potency was superior and only equaled by fibronectin. Next, the majority of the newly recruited osteoblast lineage cells positioned immediately next to the osteoclasts exhibit uPARAP/Endo180, an endocytic collagen receptor reported to be involved in collagen internalization and cell migration in various cell types, and whose inactivation is reported to lead to lack of bone formation and skeletal deformities. In the present study, an antibody directed against this receptor inhibits collagen internalization in osteoblast lineage cells and decreases to some extent their migration to surface-bound collagen in the transmembrane migration assay. These complementary observations lead to a model where collagen demineralized by osteoclasts attracts surrounding osteoprogenitors onto eroded surfaces, and where the endocytic collagen receptor uPARAP/Endo180 contributes to this migration, probably together with other collagen receptors. This model fits recent knowledge on the position of osteoprogenitor cells immediately next to remodeling sites in adult human cancellous bone.

Correlation between Absence of Bone Remodeling Compartment Canopies, Reversal Phase Arrest, and Deficient Bone Formation in Post-Menopausal Osteoporosis

Bone remodeling compartments (BRCs) were recently recognized to be present in patients with primary hyperparathyroidism and critical for bone reconstruction in multiple myeloma and endogenous Cushings syndrome. The BRCs are outlined by a cellular canopy separating the bone remodeling events on the bone surface from the marrow cavity. The present study on human iliac crest biopsy specimens reveals that BRC canopies appear frequently absent above both eroded and formative surfaces in post-menopausal osteoporosis patients, and that this absence was associated with bone loss in these patients. The absence of BRC canopies above the eroded surfaces was furthermore associated with the accumulation of arrested reversal surfaces and a reduced extent of formative surfaces, which both reflect an increased incidence of aborted remodeling cycles. Moreover, the absence of BRC canopies above formative surfaces was associated with a shift in the osteoblast morphological characteristics, from cuboidal to flattened. Collectively, this study shows that the BRCs are unique anatomical structures implicated in bone remodeling in a widespread disease, such as post-menopausal osteoporosis. Furthermore, it particularly highlights the role of the BRC canopies to make the reversal phase progressing toward initiation of matrix deposition, thereby preventing bone loss.

The relationship between ultra-short telomeres, aging of articular cartilage and the development of human hip osteoarthritis

INTRODUCTIONnUltra-short telomeres caused by stress-induced telomere shortening are suggested to induce chondrocyte senescence in human osteoarthritic knees. Here we have further investigated the role of ultra-short telomeres in the development of osteoarthritis (OA) and in aging of articular cartilage in human hips.nnnMATERIALS AND METHODSnCartilage was obtained from four different distances of the central weight-bearing area in human femoral heads (14 OA and 9 non-OA). Samples were split into three: one for quantification of ultra-short single telomeres by Universal STELA and mean telomere length measurement by Q-PCR; one for histological grading of OA, and one for immunohistochemical staining.nnnRESULTSnLoad of ultra-short telomeres increased closer to the central weight-bearing area and correlated with cartilage degradation in both OA and non-OA samples. Mean telomere length decreased with decreasing distance to the central weight-bearing area, however, unexpectedly increased in the most central zone. This increase was associated with immunohistochemical findings of cells expressing markers characteristic of progenitor-like cells.nnnCONCLUSIONnThese findings suggest a role of short telomeres in the development of OA and in aging of articular cartilage. Furthermore, progenitor-like cells with long telomeres may be recruited to the most damaged areas of the cartilage.

Nursing in fast-track total hip and knee arthroplasty: A retrospective study

AIMnTo describe the increased activity in total hip arthroplasty (THA) and total knee arthroplasty (TKA) from 2002 to 2012 in a single orthopaedic department, the organisation of fast-track and its consequences for nursing care.nnnMETHODSnRetrospective, descriptive design. Data collection; from the hospital administrative database, local descriptions of fast-track, personal contact and discussion with staff.nnnRESULTSnThe number of operations increased threefold from 351 operations in 2002 to 1024 operations in 2012. In 2012, THA/TKA patients had a postoperative mean LOS of 2.6/2.8 days. Nurses had gained tasks from surgeons and physiotherapists and thus gained more responsibility, for example, for pain management and mobilisation. Staffing levels in the ward in 2002 and 2012 were almost unchanged; 16.0 and 15.8 respectively. Nurses were undertaking more complicated tasks.nnnCONCLUSIONnNursing care must still focus on the individual patient. Nurses need to have enough education to manage the complex tasks and increased responsibility. To prevent undesirable outcomes in the future, there is a need to pay attention to the nursing quality in balance with the nursing budget. It may, therefore, be considered a worthwhile investment to employ expert/highly qualified professional nurses in fast-track THA and TKA units.

Patients’ experiences during the first 12 weeks after discharge in fast-track hip and knee arthroplasty – a qualitative study

BACKGROUNDnDue to the shortened length of stay in fast-track total hip and knee arthroplasty, patients must at a very early stage following surgery take responsibility for their postoperative care and treatment. It is important to establish if this treatment modality of fast-track is not only cost-effective, but meets patients expectations and needs.nnnAIMnTo explore the lived experience of patients in fast-track total hip and knee arthroplasty during the first 12 weeks after discharge.nnnMETHODSnA phenomenological-hermeneutic approach was used inspired by Ricoeurs theory of narrative and interpretation. Data were collected through semi-structured interviews with 8 patients 2 and 12 weeks after discharge.nnnFINDINGSnThrough the structural analysis 3 themes emerged: 1) Dealing with transition between hospital and home, 2) Pain and self-management of medication, 3) Challenges in rehabilitation.nnnCONCLUSIONnPatients appreciated only 1 or 2 days in hospital. However, they were not sufficiently involved in the discharge planning. There was a feeling of uncertainty and being left on their own after discharge, which could affect their pain management and recovery at home. There is a need to develop in partnership with each individual patient a post discharge plan of care and rehabilitation to meet their individual needs, preferences and mode of motivation.