Thelonius Hawellek

Clinical, radiographic and biochemical characteristics of adult hypophosphatasia

SummaryIn this study, we report on clinical, radiographic and biochemical characteristics of 38 patients with adult hypophosphatasia. High-resolution peripheral quantitative computed tomography showed alterations of bone microstructure in a subgroup of 14 patients. Pyridoxal-5-phosphate levels correlated with the occurrence of fractures and the number of symptoms.IntroductionHypophosphatasia (HPP) is a rare disorder with a wide range of clinical manifestations. A reduced enzymatic activity of alkaline phosphatase (ALP) is the key marker of the disease, causing an accumulation of ALP substrates such as pyridoxal-5-phosphate (PLP). The purpose of this retrospective study was to further characterize adult onset HPP.MethodsWe assessed clinical, radiographic and laboratory characteristics of 38 adult patients with HPP. Diagnosis of HPP was established by the combination of low-serum ALP, raised PLP levels and typical symptoms and was genetically confirmed in 32 patients. Dual-energy X-ray absorptiometry (DXA) and laboratory data were available in most patients. High-resolution peripheral quantitative computed tomography (HR-pQCT) was performed in 14 patients.ResultsClinical characteristics included a wide spectrum of symptoms. A history of fracture was present in 15 patients (39%). Twenty-one patients (55%) complained about recurring headaches, 23 patients (61%) had recurring muscle pain, 4 patients (11%) suffered from severe muscle weakness and 18 patients (47%) showed dental abnormalities. Z-scores assessed by DXA were only slightly reduced in most adult HPP patients. HR-pQCT of 14 patients showed microstructural changes of trabecular and cortical bone compared to reference values of healthy subjects. The occurrence of fractures and multiple symptoms (>2 typical HPP symptoms) were associated with significantly elevated levels of PLP.ConclusionAdult HPP presents with a wide range of clinical symptoms and is not associated with low bone mass in general. PLP seems to be a good marker for disease severity in adult patients as its level is correlated with the occurrence of fractures and number of symptoms.

Articular cartilage calcification of the humeral head is highly prevalent and associated with osteoarthritis in the general population.

Articular cartilage calcification is considered a pathological albeit incompletely understood process which is known to be associated with osteoarthritis of the knee and hip. The goal of this study was to determine the prevalence of articular cartilage calcification of the shoulder as a non‐weight‐bearing joint and to analyze the interrelationship of calcification with age and histological severity of shoulder osteoarthritis in the general population. In a cross‐sectional study of 180 humeral heads from 90 donors (n = 49 male, n = 41 female; mean age 62.7 years [20–93]), cartilage calcification of the humeral head was quantified by digital contact radiography (DCR). Histological OA grade (OARSI) was determined and structural equation modeling (SEM) was used to analyze the interrelationship of cartilage calcification, OARSI and age. The prevalence of articular cartilage calcification was 98.9% (95%CI: [93.96%, 99.97%]) and was independent of gender (p = 0.55). Cartilage calcification of one shoulder correlated significantly with that of the contralateral side (r = 0.61, 95%CI: [0.46, 0.73], p < 0.001). SEM demonstrated significant associations between histological OA grade and cartilage calcification (r = 0.55, p = 0.039), between histological OA grade and age (β = 0.59, p < 0.001) but not between age and cartilage calcification (β = 0.24, p = 0.116). In conclusion, the prevalence of shoulder cartilage calcification in the general population is higher than anticipated. The high prevalence, its concomitant bilateral manifestation and the association between the amount of cartilage calcification and OA severity, but not age, suggest that cartilage calcification is a systemically driven process with early onset in life and may be a causative factor in the pathogenesis of OA.

Disease Duration and Stage Influence Bone Microstructure in Patients With Primary Biliary Cholangitis: BONE MICROSTRUCTURE IN PBC PATIENTS

Primary biliary cholangitis (PBC) is known to be a major risk factor for osteoporosis reflected by a reduction of bone mineral density (BMD). However, both the extent of the macro‐ and microstructural alterations of bone as well as the causative factors are unknown. We have retrospectively analyzed a total of 96 patients with PBC and 53 healthy controls matched for age, sex, and body mass index. In addition to dual‐energy X‐ray absorptiometry (DXA) measurements at the lumbar spine and hip, high‐resolution peripheral quantitative computed tomography (HR‐pQCT) was used to assess the geometric, volumetric, and microstructural changes of bone at the distal radius and tibia. Furthermore, serum analyses and measures of disease duration and stage including transient elastography were performed. Total, cortical, and trabecular volumetric BMD as well as geometric parameters were significantly reduced in PBC patients. Microstructural analysis revealed a significantly lower cortical thickness (p < 0.001) and bone volume per tissue volume (p < 0.001) in the radius and tibia but unchanged trabecular number in patients with PBC (radius: p = 0.42; tibia: p = 0.12). Multivariate regression models pointed out that disease duration and stage are the primary factors that are independently associated with bone loss in PBC. A subgroup analysis of patients with additional autoimmune hepatitis (AIH) revealed no significant changes in bone structure compared with PBC only. Taken together, PBC patients demonstrate severe alterations in bone microstructure that are positively associated with disease duration and stage. By applying HR‐pQCT in the distal radius and tibia, a combined bone loss syndrome expressed by a predominant decrease in BMD and cortical thickness could be detected.

Microcalcification of lumbar spine intervertebral discs and facet joints is associated with cartilage degeneration, but differs in prevalence and its relation to age

Cartilage calcification (CC) is associated with degeneration in non‐vertebral joints, but little is known about CC and lumbar vertebral joints. The goal of this study was to analyze the prevalence of CC in lumbar facet joints (FJ) and intervertebral discs (IVD) and its relation to cartilage degeneration and age in a non‐selected cohort of the general population. The segment L4/5 of 85 consecutive donors (mean age 61.9 years) was analyzed by high‐resolution imaging digital‐contact radiography (DCR). Quantification was achieved by measuring CC in % of total cartilage area. Histological degeneration of FJs and IVDs was determined by OARSI and Boos scores. Prevalence of CC was 36.5% for FJ (95%CI (0.26, 0.48)) and 100% for IVD (95%CI (0.96, 1.00)). The amount of IVD CC (3.36% SD ± 7.14) was 16.3 times higher (p < 0.001) than that of the FJ (0.23% SD ± 0.53) and independent of each other (p = 0.07). The amount of FJ CC correlated significantly with FJ and IVD degeneration (FJ r = 0.44, p = 0.01, IVD r = 0.49, p = 0.006) while the amount of IVD CC correlated only with IVD degeneration (r = 0.54, p < 0.001). Age correlated with IVD CC (rs = 0.35, p < 0.001), but not FJ CC (rs = 0.04, p = 0.85). We conclude that IVD fibrocartilage is particularly prone to calcification. A causal relationship between lumbar CC and degeneration is possible, but the clear differences in IVD fibrocartilage CC and FJ synovial joint CC in regard to prevalence and in relation to age point to a differential role of CC in single compartments of the respective motion segment in lumbar spine degeneration.

Autologous bridging of rotator cuff tears with a hamstring tendon patch. A cadaver feasibility study and biomechanical testing

a ATOS Klinik Fleetinsel Hamburg, Department of Shoulder and Elbow Surgery, Admiralitätstrasse 3-4, 20459 Hamburg, Germany b Institute of Biomechanics, University Hospital Hamburg-Eppendorf, Lottestrasse 59, 22529 Hamburg, Germany c Department of Orthopaedics, University Hospital Hamburg-Eppendorf, Eppendorfer Landstrasse 60, 20249 Hamburg, Germany d Department of Legal Medicine, University Hospital Hamburg-Eppendorf, Butenfeld 34, 22529 Hamburg, Germany e Department of Orthopaedics, University Hospital, Medical Faculty, Heinrich-Heine-University Düsseldorf, Moorenstr. 5, 40255 Düsseldorf, Germany

Inter-site variability of the osteocyte lacunar network in the cortical bone underpins fracture susceptibility of the superolateral femoral neck

BACKGROUND The osteocytic lacunar network is considered to be an integral player in the regulation of bone homeostasis, and reduction in osteocytes is associated with reduced bone strength. Here, we analyzed site-specific patterns in osteocyte characteristics and matrix composition in the cortical compartment of the femoral neck to reveal the structural basis of its fragility. METHODS Cross-sections of the human femoral neck - one of the most common fracture sites - were acquired from 12 female cadavers (age 34-86 years) and analyzed with backscattered scanning electron microscopy and high-resolution micro-computed tomography (μ-CT). The 2D/3D density and size of the osteocyte lacunae as well as bone mineral density distribution (BMDD) were measured in two regions subject to different biomechanical loads in vivo: the inferomedial (medial) region (habitually highly loaded in compression) and the superolateral (lateral) region (lower habitual loading intensity). Using quantitative polarized light microscopy, collagen fiber orientation was quantified in these two regions, accordingly. RESULTS In 2D measurements, the inferomedial region displayed lower mineralization heterogeneity, 19% higher osteocyte lacunar density (p = 0.005), but equal lacunar size compared to the superolateral region. 3D measurements confirmed a significantly higher osteocyte lacunar density in the inferomedial region (p = 0.015). Osteocyte lacunar density decreased in aged individuals, and inter-site differences were reduced. Site-specific osteocyte characteristics were not accompanied by changes in collagen fiber orientation. CONCLUSIONS Since osteocyte characteristics may provide valuable insights into bone mechanical competence, the variations in osteocyte properties might reflect the increased fracture susceptibility of the superolateral neck.

Calcification of the acetabular labrum of the hip: prevalence in the general population and relation to hip articular cartilage and fibrocartilage degeneration

BackgroundMeniscal calcification is considered to play a relevant role in the pathogenesis of osteoarthritis of the knee. Little is known about the biology of acetabular labral disease and its importance in hip pathology. Here, we analyze for the first time the calcification of the acetabular labrum of the hip (ALH) and its relation to hip cartilage degeneration.MethodsIn this cross-sectional post-mortem study of an unselected sample of the general population, 170 ALH specimens and 170 femoral heads from 85 donors (38 female, 47 male; mean age 62.1 years) were analyzed by high-resolution digital contact radiography (DCR) and histological degeneration grade. The medial menisci (MM) from the same 85 donors served as an intra-individual reference for cartilage calcification (CC). Scanning electron microscopy (SEM), energy dispersive analysis (ED) and Raman spectroscopy were performed for characterization of ALH CC.ResultsThe prevalence of CC in the ALH was 100% and that in the articular cartilage of the hip (ACH) was 96.5%. Quantitative analysis revealed that the amount of ALH CC was higher than that in the ACH (factor 3.0, p < 0.001) and in the MM (factor 1.3, p < 0.001). There was significant correlation between the amount of CC in the fibrocartilage of the left and right ALH (r = 0.70, p < 0.001). Independent of age, the amount of ALH CC correlated with histological degeneration of the ALH (Krenn score) (r = 0.55; p < 0.001) and the ACH (Osteoarthritis Research Society International (OARSI), r = 0.69; p < 0.001). Calcification of the ALH was characterized as calcium pyrophosphate dihydrate deposition.ConclusionThe finding that ALH fibrocartilage is a strongly calcifying tissue is unexpected and novel. The fact that ALH calcification correlates with cartilage degeneration independent of age is suggestive of an important role of ALH calcification in osteoarthritis of the hip and renders it a potential target for the prevention and treatment of hip joint degeneration.

Labral calcification in end‐stage osteoarthritis of the hip correlates with pain and clinical function

The acetabular labrum of the hip (ALH) is recognized as a clinically important structure, but knowledge about the pathophysiology of this fibrocartilage is scarce. In this prospective study we determined the prevalence of ALH calcification in patients with end‐stage osteoarthritis (OA) and analyzed the relationship of cartilage calcification (CC) with hip pain and clinical function. Cohort of 80 patients (70.2 ± 7.6years) with primary OA scheduled for total hip replacement. Harris Hip Score (HHS) was recorded preoperatively. Total ALH and femoral head (FH) were sampled intraoperatively. CC of the ALH and FH was analyzed by high‐resolution digital contact radiography. Histological degeneration of the ALH (Krenn‐Score) and FH (OARSI‐Score) was determined. Multivariate linear regression model and partial correlation analyses were performed. The prevalence of cartilage calcification both in the ALH and FH was 100%, while the amount of CC in the ALH was 1.55 times higher than in the FH (p < 0.001). There was a significant inverse regression between the amount of calcification of both the ALH and the FH and preoperative HHS (βALH = −2.1, p = 0.04), (βFH = −2.9, p = 0.005), but pain was influenced only by ALH calcification (βALH = −2.7, p = 0.008). Age‐adjusted, there was a significant correlation between cartilage calcification and histological degeneration (ALH:rs = 0.53, p < 0.001/FH: rs = 0.30, p = 0.007). Fibrocartilage and articular cartilage calcification are inseparable pathological findings in end‐stage osteoarthritis of the hip. Fibrocartilage calcification is associated with poor and painful hip function. Clinical significance: ALH fibrocartilage appears to be particularly prone to calcification, which may explain higher pain levels in individuals with a high degree of ALH calcification independent of age and histological degeneration.