P. H. Pennekamp

Osteoporosis in haemophilia - an underestimated comorbidity?

Summary.  A relationship between haemophilia and osteoporosis has been suggested, leading to the initiative for a larger study assessing this issue. Bone mineral density (BMD) was measured by osteodensitometry using dual energy X‐ray absorptiometry (DEXA) in 62 male patients with severe haemophilia A; mean age 41 ± 13.1 years, mean body mass index (BMI) 23.5 ± 3.6 kg m−2. Using the clinical score suggested by the World Federation of Hemophilia, all patients were assessed to determine the severity of their arthropathy. A reduced BMD defined as osteopenia and osteoporosis by World Health Organization criteria was detected in 27/62 (43.5%) and 16/62 (25.8%) patients, respectively. Fifty‐five of sixty‐two (88.7%) patients suffered from haemophilic arthropathy. An increased number of affected joints and/or an increased severity were associated with lower BMD in the neck of femur. Pronounced muscle atrophy and loss of joint movement were also associated with low BMD. Furthermore, hepatitis C, low BMI and age were found to be additional risk factors for reduced BMD in the haemophiliac. Our data shows that in haemophilic patients osteoporosis represents a frequent concomitant observation. The main cause for reduced bone mass in the haemophiliac is most probably the haemophilic arthropathy being typically associated with chronic pain and loss of joint function subsequently leading to inactivity. Further studies including control groups are necessary to elucidate the impact of comorbidities such as hepatitis C or HIV on the development of osteoporosis in the haemophiliac.

Soluble ions more than particulate cobalt-alloy implant debris induce monocyte costimulatory molecule expression and release of proinflammatory cytokines critical to metal-induced lymphocyte reactivity.

Aseptic osteolysis has been associated with excessive immune reactivity to particulate implant debris; however, innate and adaptive immune mechanisms that underlie implant debris reactivity remain incompletely understood. Although particulate debris has been implicated as the major type of implant debris mediating macrophage-induced osteolysis, the degree to which metal ions affect a proinflammatory response (if at all) remains unknown. We hypothesized that both soluble and particulate metal implant debris will induce proinflammatory responses in human monocytes resulting in cytokine production and elevated expression of T cell costimulatory molecules, facilitating adaptive immune responses. We tested this hypothesis by characterizing the response of a human monocyte cell line (THP-1), isolated primary human monocytes and PBMCs challenged with Co-Cr-Mo alloy particles and soluble cobalt, chromium, molybdenum, and nickel ions. Our results indicate that soluble cobalt, nickel, and molybdenum can induce monocyte up-regulation of T cell costimulatory molecules (CD80, CD86, ICAM-1) in human monocytes/macrophages. Furthermore, cobalt, molybdenum ions, and Co-Cr-Mo alloy particles similarly induce elevated secretion of IL-1beta, TNFalpha, and IL-6. Antibody blockade of CD80 and CD86, crucial secondary molecules for adaptive responses, abrogated lymphocyte reactivity to metal challenge in metal reactive subjects. Also the addition of IL-1 receptor antagonist (IL-1ra), (which indirectly blocks pro-IL-1beta and thus IL-1beta release), significantly reduced lymphocyte reactivity in metal-reactive subjects. Thus, both soluble and particulate metal implant debris induce monocyte/macrophage proinflammatory responses that are metal and individual specific. This suggests metal-induced up-regulation of costimulatory molecules and proinflammatory cytokine production is necessary to induce lymphocyte activation/proliferation to metal implant debris.

CRP and leukocyte-count after lumbar spine surgery: fusion vs. nucleotomy

Background Despite the fact that C-reactive protein (CRP) levels and white blood cell (WBC) count are routine blood chemistry parameters for the early assessment of wound infection after surgical procedures, little is known about the natural history of their serum values after major and minimally invasive spinal procedures. Methods Pre- and postoperative CRP serum levels and WBC count in 347 patients were retrospectively assessed after complication-free, single-level open posterior lumbar interlaminar fusion (PLIF) (n = 150) for disc degeneration and spinal stenosis and endoscopically assisted lumbar discectomy (n = 197) for herniated lumbar disc. Confounding variables such as overweight, ASA classification, arterial hypertension, diabetes mellitus, and perioperative antibiotics were recorded to evaluate their influence on the kinetics of CRP values and WBC count postoperatively. Results In both procedures, CRP peaked 2–3 days after surgery. The maximum CRP level was significantly higher after fusion: mean 127 (SD 57) (p < 0.001). A rapid fall in CRP within 4–6 days was observed for both groups, with almost normal values being reached after 14 days. Only BMI > 25 and long duration of surgery were associated with higher peak CRP values. WBC count did not show a typical and therefore interpretable profile. Conclusion CRP is a predictable and responsive serum parameter in postoperative monitoring of inflammatory responses in patients undergoing spine surgery, whereas WBC kinetics is unspecific. We suggest that CRP could be measured on the day before surgery, on day 2 or 3 after surgery, and also between days 4 and 6, to aid in early detection of infectious complications.

Magnetic Resonance Imaging Findings of the Lumbar Spine in Elite Horseback Riders: Correlations With Back Pain, Body Mass Index, Trunk/Leg-Length Coefficient, and Riding Discipline

Background Most orthopaedic problems experienced by competitive horseback riders are related to pain in the lower back, hip joint, and hamstring muscles. Riders—especially, show jumpers—are frequently hampered in their performance because of lumbar pain. To date, there has been no research into lumbar disk degeneration in elite competitive riders. Hypothesis Competitive horseback riding accelerates lumbar disk degeneration. Study Design Cross-sectional study; Level of evidence, 3. Methods Fifty-eight elite riders (18 men, 40 women; mean age, 32.4 years) and a control group of 30 nonriding volunteers (17 men, 13 women; mean age, 28.7 years) were evaluated for lumbar disk degeneration, cross-sectional area of paraspinal muscles, spondylolysis, and spondylolisthesis, using magnetic resonance imaging (MRI). The prevalence of disk degeneration between the 2 groups was compared, and the relationship was investigated between low back pain (LBP), riding discipline, body mass index (BMI), trunk/leg-length coefficient, and MRI results. Results Eighty-eight percent of elite riders (n = 51) had a history of LBP, versus 33% of the controls (P < .05). There was no statistical difference for the prevalence of LBP among the different riding disciplines. However, there was a high rate of pathologic T2 signal intensity of the lumbar intervertebral disk among riders—specifically, dressage riders—yet no significant increase when compared with controls. History of LBP symptoms, riding discipline, BMI, and trunk/leg-length ratio had no significant effect on the development of lumbar disk degeneration. Occult fractures of the pars interarticularis and manifest spondylolysis were not seen for any rider. Two controls had spondylolisthesis Meyerding grade 1 not associated with back pain. Conclusion Although riders have a high prevalence of LBP, there is no conclusive MRI evidence to suggest that the cause lies in undue disk degeneration, spondylolysis, spondylolisthesis, or pathologic changes of the paraspinal muscles of the lumbar spine.

Total ankle replacement in patients with haemophilia and virus infections--a safe alternative to ankle arthrodesis?

Despite reliable results of ankle fusion for advanced haemophilic arthropathy, total ankle replacement (TAR) may be functionally advantageous. There is only very limited literature data available on TAR in patients with haemophilia. The objective of this study is to evaluate the short‐ and mid‐term results after TAR in patients with end‐stage haemophilic ankle arthropathy and concomitant virus infections. In a retrospective study, results after eleven TAR in 10 patients with severe (n = 8) and moderate (n = 2) haemophilia (mean age: 49 ± 7 years, range, 37–59) were evaluated at a mean follow‐up of 3.0 years (range, 1.2–5.4). Nine patients were positive for hepatitis C, five were HIV‐positive. Range of motion (ROM), AOFAS‐hindfoot‐score, pain status (visual analogue scale, VAS) as well as patient satisfaction were evaluated. In two cases deep prosthesis infection occurred leading to the removal of the implant. In the remaining eight patients the mean AOFAS score improved significantly from 21.5 to 68.0 points (P < 0.0005), the VAS score decreased significantly from 7.6 to 1.9 points (P < 0.0005). ROM increased from 23.2 to 25.0 degrees (P = 0.51). At final follow‐up all patients without any complications were satisfied with the postoperative results. Radiographic examination did not reveal any signs of prosthetic loosening. TAR is a viable surgical treatment option in patients with end‐stage ankle osteoarthritis due to haemophilia. It provides significant pain relieve and high patient satisfaction. However, due to the increased risk of infection and lack of long‐term results, TAR particularly in patients with severe haemophilia and virus infections should be indicated carefully.

MALDI imaging of predictive ferritin, fibrinogen and proteases in haemophilic arthropathy.

Arthropathy as a result of repeated joint bleeding is a severe complication in patients with haemophilia. In the evaluation of synovial tissue specimens, histology alone is non‐specific and there is considerable morphological overlap with other joint diseases. Formalin‐fixed paraffin‐embedded specimens are available in pathological institutes and can be studied to understand the pathogenesis of haemophilic arthropathy. A powerful technique to identify hundreds of proteins in a tissue section combining proteomics with morphology is imaging mass spectrometry (IMS). We determined whether matrix‐assisted laser desorption/ionization (MALDI) IMS can be used to identify and map protein signatures in the synovial tissue of patients with haemophilic arthropathy. MALDI IMS was applied to synovial tissue of six patients with haemophilic arthropathy. We detected several peaks predictive in mass with ferritin light (m/z 1608) and heavy chain (m/z 1345), alpha‐ (m/z 1071) and beta (m/z 1274) haemoglobin subunits, truncated coagulation factor VIII peptide (m/z 1502, 1176), beta‐ and gamma fibrinogen peptides (m/z 980, 1032, 1117 and 1683), and annexin A2 (m/z 1111, 1268, 1460, 2164). In addition, the distribution of these proteins in synovial tissue sections was demonstrated. MALDI IMS identified and mapped specific proteins in the synovial membrane of patients with haemophilic arthropathy known to be involved in the pathogenesis of other joint diseases. This technique is a powerful tool to analyse the distribution of proteins in synovial tissue sections.

Achilles tendon lengthening for ankle equinus deformity in hemophiliacs: 23 patients followed for 1–24 years

Background Bleeding in the calf or ankle joint may lead to ankle equinus deformity, particularly in childhood and during adolescence. We assessed the long-term functional and radiographic results after Achilles tendon lengthening for ankle equinus deformity in hemophiliacs. Patients and methods Between 1975 and 1986, 30 hemophilic patients with pes equinus were surgically managed by Achilles tendon lengthening. Of these, 23 were followed up prospectively twice a year for an average of 13 (1–24) years. The mean age at operation was 29 (12–46) years. The clinical results were documented according to the score of the Advisory Committee of the World Federation of Hemophilia (WFH), while radio-graphs were evaluated using the Pettersson score. On average, preoperative ankle equinus deformity was 21 (5–55) degrees. Mean range of motion was 21 (5–42) degrees prior to surgery. Results At the first postoperative examination 1 year after surgery, 21/23 cases were improved, and 9/21 reached dorsiflexion to at least neutral position. At the last follow-up, ankle equinus deformity was 10 (4–20) degrees on average. 20/23 patients still showed significant improvement compared to their condition before surgery. 7 patients still had complete correction of the equinus deformity, while mean range of motion decreased constantly over the observation period. The clinical score was significantly improved 1 year after surgery and diminished only slightly afterwards. Radio-graphic outcome deteriorated, with scores rising from 4.3 (1–10) points preoperatively to 7.3 (3–12) points at last follow-up. Interpretation Most patients treated for hemophilic pes equinus by Achilles tendon lengthening experienced long-term benefit concerning the equinus deformity, but gradually lost overall movement of the ankle joint. Progression of the ankle arthropathy cannot be hindered. ▪

Outcome after total knee arthroplasty in haemophilic patients with stiff knees

Advanced haemophilic arthropathy of the knee is associated with progressive joint stiffness. Results after total knee arthroplasty (TKA) in stiff knees are considered to be inferior compared to those with less restricted preoperative range of motion (ROM). There is only very limited data on the results of primary TKA in haemophilic patients with stiff knees.

Implant wear and aseptic loosening. An overview

ZusammenfassungDer Verschleiß von Gelenkimplantaten unterliegt multifaktoriellen Einflussgrößen, die in Ihrem Zusammenspiel auch bei nominell identischen Gleitpaarungen höchst unterschiedliche Partikelmengen und -formen generieren können. Die biologische Reaktion und damit letztendlich der klinische Erfolg des Implantats wird dabei von den speziellen Partikeleigenschaften beeinflusst. Eine dauerhafte Implantatversorgung bedingt einen optimierten Kompromiss zwischen Material, Design, Operationsmethode und patientenspezifischen Faktoren.AbstractWear of total joint implants is multifactorial in nature. Even for identical materials and geometries, the interaction of those parameters can generate different numbers of particles as well as different particle sizes and shapes. These different wear-particle characteristics will directly influence the biological response to an implant and thereby its clinical success. The long-term success of a total joint replacement requires an optimized compromise among implant material, design, surgical procedure, and biological performance.Wear of total joint implants is multifactorial in nature. Even for identical materials and geometries, the interaction of those parameters can generate different numbers of particles as well as different particle sizes and shapes. These different wear-particle characteristics will directly influence the biological response to an implant and thereby its clinical success. The long-term success of a total joint replacement requires an optimized compromise among implant material, design, surgical procedure, and biological performance.

Verschleiß und aseptische Prothesenlockerung

ZusammenfassungDer Verschleiß von Gelenkimplantaten unterliegt multifaktoriellen Einflussgrößen, die in Ihrem Zusammenspiel auch bei nominell identischen Gleitpaarungen höchst unterschiedliche Partikelmengen und -formen generieren können. Die biologische Reaktion und damit letztendlich der klinische Erfolg des Implantats wird dabei von den speziellen Partikeleigenschaften beeinflusst. Eine dauerhafte Implantatversorgung bedingt einen optimierten Kompromiss zwischen Material, Design, Operationsmethode und patientenspezifischen Faktoren.AbstractWear of total joint implants is multifactorial in nature. Even for identical materials and geometries, the interaction of those parameters can generate different numbers of particles as well as different particle sizes and shapes. These different wear-particle characteristics will directly influence the biological response to an implant and thereby its clinical success. The long-term success of a total joint replacement requires an optimized compromise among implant material, design, surgical procedure, and biological performance.Wear of total joint implants is multifactorial in nature. Even for identical materials and geometries, the interaction of those parameters can generate different numbers of particles as well as different particle sizes and shapes. These different wear-particle characteristics will directly influence the biological response to an implant and thereby its clinical success. The long-term success of a total joint replacement requires an optimized compromise among implant material, design, surgical procedure, and biological performance.