Ugo E. Pazzaglia

Loss of sight and sound. Could it be the hip

In September, 2007, a 58-year-old woman was admitted to our neurology department because of progressive visual and hearing loss which had started 9 months earlier. She had type 2 diabetes and hypertension, both of which were adequately controlled by medication. In 2001, she had a left hip arthroplasty which was revised in October, 2006 because of rupture of the ceramic head. 3 weeks before admission, investigations showed a mild hypothyroidism of unknown origin, which was treated with levothyroxine sodium. The neurological examination at admission showed impairment of cranial nerves II and VIII bilaterally and mild distal sensory-motor dis turbances. Laboratory investigations ruled out haema tological, infectious, neoplastic, metabolic, and immuno logical diseases. Concomitantly our patient underwent various investigations including brain MRI (showing hyperintensity of optic nerves and tracts), electromyography (showing mild lower limb nerve amplitude reduction), and acoustic and visual evoked potentials (positive for bilateral absence of brainstem acoustic responses and irregular cortical visual responses). A working diagnosis of axonal multi-neuropathy caused by a presumed immune-mediated vasculitis was made and the patient was given prednisone (50 mg/day) for 2 months with little improvement. By December, 2007, our patient became completely blind, severely deaf, and wheel-chair bound because of lower limb hyposthenia. Tests for immune-mediated process remained negative and the case was referred to toxicology for further investigation. Unexpectedly, raised concentrations of cobalt and chromium were found in diff erent biological samples (cobalt: 24 h urine collection 1187 μg/L [0·1–1·5], blood 549 μg/L [0·05–2·7], plasma 90 μg/L [0·1–0·6], CSF 11·4 μg [0·05–0·15]; chromium: 24 h urine collection 510 μg/L [0·05–2·2], blood 54 μg/L [0·1–0·5], plasma 210 μg/L [0·1–0·5], CSF 4·4 μg/L [0·01–0·2]). Cobalt-chromium poisoning due to metal wear debris from her hip prosthesis was proposed, although radiology, including CT, showed no sign of prosthesis loosening. In February, 2008, several metal ion chelating treatments were given with edetic acid. Although metal ion concentrations decreased, neurological improve ment was negligible. Therefore, in April, 2008, resection arthroplasty was done. During surgery infi ltration of the peri-prosthesic tissue by metallic debris was evident (fi gure A); analysis of peri-prosthetic fl uids showed high concentrations of cobalt and chromium, and the removed prosthesis showed wear of the head and neck (fi gure B), supporting the hypothesis of endogenous cobalt-chromium poisoning. During the following 8 months the patient showed progressive improvement, although vision only partially improved. Metal ion concentrations decreased but remained higher than reference values at the last follow-up in November, 2008. The role of cobalt or cobalt-chromium on human tissues has not been defi nitively established. Cobalt can produce various toxicological eff ects including local respiratory symptoms due to inhalation of cobalt containing dusts, and systemic eff ects (thyroiditis, cardiomyopathy, erythropoiesis). Neuro logical toxicity, mainly optic atrophy, nerve deafness, and limb paraesthesia, has been occasionally reported in association with exogenous exposure. Neuro logical toxicity as a reult of endogenous exposure (mainly associated with metal prostheses) has been described. Cobalt can induce a hypoxia-like eff ect, possibly targeting mitochondria; of note, our patient’s symptoms were similar to those observed in some mitochondrial cytopathies. Total hip replacement and hip resurfacing arthroplasty are widely used therapeutic procedures; longer-term follow-up would be necessary to evaluate adverse chronic systemic eff ects due to prolonged exposure to high serum cobalt concentrations. In addition to orthopaedic evaluation, careful neurological and toxicological examinations are recommended whenever a patient with a metallic prosthesis complains of visual loss, hearing disturbance, limb weakness, numbness, or paraesthesia, even in the absence of local osteoarticular symptoms.

Metal ions in body fluids after arthroplasty

We measured levels of metal ions in urine and plasma of 17 patients 7-15 years after they had a Co-Cr-Mo alloy total hip replacement. They had higher levels of cobalt and chromium than controls. No case of skin sensitivity to the investigated metals was observed. The values of cobalt and chromium in plasma and urine were considerably lower than in professionally exposed groups and do not represent a toxic hazard for the patients.

Cobalt, chromium and molybdenum ions kinetics in the human body: data gained from a total hip replacement with massive third body wear of the head and neuropathy by cobalt intoxication

IntroductionA patient with a total hip replacement developed optic, acoustic and peripheral neuropathy from metal ions intoxication, due to the wear products released from the prosthesis. Subsequently the kinetics of the metal ions was studied.Materials and methodsMassive wear and acute intoxication allowed a study of the metal ions kinetics and of EDTA treatment.ResultsPlasma and other organic fluids were saturated by each of the metal ions released from the exposed surface according to the solubility of each ion; a larger fraction of Co ions was bound within red cells, while the plasmatic fraction appeared more movable. In a patient with a prosthesis subjected to wear, the ions released are from the prosthetic and from the debris surface (spread in the body). The latter is a function of the number and size of particles.DiscussionRevision of the prosthesis from the point of view of the metal ions kinetics corresponded to a reduction of the releasing surface because of debris washed out by irrigation and tissue excision; however, the metal particles spread by lymphatic circulation continued to release ions even though the source of wear had been removed. Early diagnosis of high metal wear can be ascertained with mass spectrometry and after revision high levels of metal ions can only be reduced with repeated chelating treatment. It is preferable not to revise fractured ceramic components with a polyethylene–metal articulation.

Anatomy of the intracortical canal system: scanning electron microscopy study in rabbit femur.

The current model of compact bone is that of a system of longitudinal (Haversian) canals connected by transverse (Volkmann’s) canals. Models based on histology or microcomputed tomography lack the morphologic detail and sense of temporal development provided by direct observation. Using direct scanning electron microscopy observation, we studied the bone surface and structure of the intracortical canal system in paired fractured surfaces in rabbit femurs, examining density of canal openings on periosteal and endosteal surfaces, internal network nodes and canal sizes, and collagen lining of the inner canal system. The blood supply of the diaphyseal compact bone entered the cortex through the canal openings on the endosteal and periosteal surfaces, with different morphologic features in the midshaft and distal shaft; their density was higher on endosteal than on periosteal surfaces in the midshaft but with no major differences among subregions. The circumference measurements along Haversian canals documented a steady reduction behind the head of the cutting cone but rather random variations as the distance from the head increased. These observations suggested discontinuous development and variable lamellar apposition rate of osteons in different segments of their trajectory. The frequent branching and types of network nodes suggested substantial osteonal plasticity and supported the model of a network organization. The collagen fibers of the canal wall were organized in intertwined, longitudinally oriented bundles with 0.1- to 0.5-μm holes connecting the canal lumen with the osteocyte canalicular system.

Morphometric Analysis of the Canal System of Cortical Bone: An Experimental Study in the Rabbit Femur Carried Out with Standard Histology and Micro‐CT

The osteonal pattern of cortical bone is gradually built around the intracortical vessels by the progression of the cutting cones (secondary remodelling); therefore, the central canal size can be used as index of the remodelling activity. An experimental model in the rabbit femur was used to investigate, through central canal morphometry and frequency distribution analysis, the remodelling activity, comparing the middle of the diaphysis (mid‐shaft) with the extremity (distal‐shaft) and at the same level sectors and layers of the cortex in transversal sections. The study documented a higher density of canals in the mid‐shaft than in the distal‐shaft and a higher remodelling in the distal‐shaft. There were no significant differences between dorsal, ventral, medial and lateral sectors at both mid‐shaft and distal‐shaft levels, while the number of canals was higher in the sub‐periosteal layers than in the sub‐endosteal. A lower threshold of 40 μm2 was observed in the central canal area. Sealed osteons in the midshaft were 22.43% of the total number of osteons of the central canal area between 40 and 200 μm2 and 0.44% of those of the distal‐shaft. Micro‐CT allowed a 3D reconstruction of the vascular canal system, which confirmed the branched network pattern rather than the trim architecture of the traditional representation. Some aspects like the lower threshold of the central canal size and the sealed osteons documented the plasticity of the system and its capacity for adaptation to changes in the haemodynamic conditions.

A model of the intracortical vascular system of long bones and of its organization: an experimental study in rabbit femur and tibia

The vascular anatomy of the cortical bone and the canal system are highly correlated, and the former has an important bearing on shape and microscopic lamellar structure, as it is established in the progression of the remodelling process. The classical description of a longitudinal system of canals (Havers’) connected by the transversal Volkmanns canals is the generally acknowledged model of the structural organization of the cortex. However, it is remarkably difficult to study the circulation inside the compact bone in detail owing to its hard, calcified matrix, and the methods thus far applied have represented either the bone morphology and the architecture of the canal system or the injected vessel network. In the present study, the intracortical vessel network was injected with black China ink and evidenced by transillumination of full‐thickness, decalcified hemicortices. By making use of the depth of field of the microscope objective, the three‐dimensional architecture of the network was highlighted and the morphometry of vessel size measurements and a classification of the network nodes according to the number of arms was made possible. These observations were integrated with data obtained by routine histology on decalcified sections relevant to the connections of the intracortical canal system with the outer environment, with regard to the direction of advancement of new canals and with regard to the mode of formation of the system nodes. The formation of the intracortical vessels network involved two processes: the incorporation of the periosteal network and osteonal remodelling, the latter occurring through the advancement of cutting cones followed by their own vascular loop and by concentric lamellar apposition. The two systems could be distinguished by the diameter of the vessels (the former were significantly larger) and by the network architecture (the former convoluted, and the latter longitudinally orientated and straight). Longitudinal vessels could form branches or create connections with the periosteal derived vessels that occasionally meet on the line of their advancement. They were observed entering from either inside the cortex from the metaphyses or from the endosteal surface of the marrow cavity. The combined observations from different methods of study documented a model of intracortical canal and vessel networks formed by two initially independent systems: one derived from the external, periosteal vessels, and one from metaphyseal and marrow vessels. Connections between the two were established with the advancing of cutting cones from the extremities of the diaphysis. Analysis of the system architecture and the modalities of its progressive organization suggested that the direction of advancement of a forming canal does not necessarily correspond to the final blood flow direction of its central vessel.

The surgical treatment of isolated mason type 2 fractures of the radial head in adults: comparison between radial head resection and open reduction and internal fixation.

Objectives: To compare the outcomes of two different surgical treatments for the management of isolated closed Mason Type 2 radial head fractures. Design: Retrospective study. The Student t test and McPearson chi-square test were used to evaluate whether there was a significance difference between the groups. Patients: Fifty-nine patients with isolated Mason Type 2 radial head fractures. Intervention: Twenty-four patients treated with radial head excision (Group I) and 35 treated with open reduction and internal fixation (Group II). Main Outcome Measurements: Clinical outcomes were assessed using the Broberg and Morrey functional rating scores and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. Orthogonal radiographs were performed on both the elbow and the wrist; these were assessed for the presence of arthritis, heterotopic ossification, and the degree of proximal radial migration. Results: The length of postoperative follow-up was 157 ± 61.84 months (Group I) and 125 ± 39.09 months (Group II). The Broberg and Morrey functional rating score was 86.21 ± 6.10 points and 95.09 ± 4.78 points, respectively. The DASH score was 21.82 ± 6.01 points and 2.81 ± 2.73 points, respectively. Radiologically moderate or severe osteoarthritis was present in the elbows of nine patients in Group I and only two patients in Group II. Conclusions: Patients with isolated Mason Type 2 radial head fractures treated by open reduction and internal fixation (Group II) had less residual pain, greater range of motion, and better strength than patients treated by radial head excision (Group I). Additionally, Group II had a lower incidence of severe posttraumatic arthritis, which contributed to improved DASH and Broberg and Morrey functional scores. These results support open reduction and internal fixation as the treatment of choice for these fractures. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

The shape modulation of osteoblast-osteocyte transformation and its correlation with the fibrillar organization in secondary osteons A SEM study employing the graded osmic maceration technique

Cortex fractured surface and graded osmic maceration techniques were used to study the secretory activity of osteoblasts, the transformation of osteoblast to osteocytes, and the structural organization of the matrix around the cells with scanning electron microscopy (SEM). A specialized membrane differentiation at the base of the cell was observed with finger-like, flattened processes which formed a diffuse meshwork. These findings suggested that this membrane differentiation below the cells had not only functioned in transporting collagen through the membrane but also in orienting the fibrils once assembled. Thin ramifications arose from the large and flat membrane foldings oriented perpendicular to the plane of the osteoblasts. This meshwork of fine filaments could not be visualized with SEM because they were obscured within the matrix substance. Their 3-D structure, however, should be similar to the canalicular system. The meshwork of large, flattened processes was no more evident in the cells which had completed their transformation into osteocytes.

The relevance of hydroxyapatite and spongious titanium coatings in fixation of cementless stems. An experimental comparative study in rat femur employing histological and microangiographic techniques.

Abstract Pure titanium rods plasma-spray coated with hydroxyapatite (HA) or porous titanium (Ti) of controlled roughness were implanted bilaterally in the distal femur of Sprague-Dawley rats to compare the extent of bone growth on the two types of coating. The relevance of other factors, like mechanical stability and biological adaptation of the bone to the insertion of a foreign body implant, were investigated in femora which were over-reamed (absence of primary fit) or reamed without insertion of the rod. Continuous tetracycline labeling for the first 30 days and for the last 2 weeks in the 90-day group was performed; histological/histometric, fluorescence and microangiographic studies were carried out on serial sections of the implanted and control femora. In the group of stable implants, HA-coated rods showed 90% integration versus 53% with Ti-coated implants (P < 0.001); in over-reamed implants neither surface bone growth nor endosteal fixation occurred, and both types of rods were surrounded by a thick layer of connective tissue. The study documented early adhesion of osteoblasts and direct deposition of bone matrix on the substrate, while on spongious titanium osteogenesis was observed only in proximity to the surface. Remodeling of the reactive, primary bone to mature, lamellar bone took the form of a capsule surrounding the implants and radial bridges connecting the latter to the endosteal surface. The number, height and thickness of these bridges appeared to be the factors determining implant stability, rather than the extent of the bony capsule on the perimeter of the implant. Integration was a function not only of mechanical conditions and surface geometry, but also of the biological response of the whole bone to changes in the vascularization pattern. The reported phenomena can be seen more easily in experimental models involving small rodents because of their fast bone turnover and revascularization, but it is expected that they take place, even at a lower speed, in clinical situations like cementless stems of total hip replacement.

A Review of the Actual Knowledge of the Processes Governing Growth and Development of Long Bones

Autoptic samples of human bones (from 8 weeks of gestation to 12 years of age) and a second group of serial, skeletal x-rays (required for pathologies not related to bone dysplasia in children from 4 months to 17 years of age) provided the material for the analysis of the physes normal growth mechanism presented in this review. Before the appearance of the ossification centers epiphyseal growth rests exclusively on chondrocytes proliferation (interstitial growth), without any detectable differentiated cellular organization. When endochondral ossification starts a defined spatial disposition of chondrocytes and a corresponding organization of the intercellular matrix is set up, so that it is possible to identify a growth vector corresponding to the columns of piled chondrocytes with direction from hypertrophic toward the proliferative cell layers. The complexity of the tubular bones growth process is well represented by the spatial arrangement of the growth vectors. In the late epiphyseal growth another mechanism is active in addition to endochondral ossification, namely, articular cartilage interstitial growth and subchondral remodelling. The knowledge of the normal mode of organization of the physis and its temporal sequence can help to better understand of the deviaton from the normal development of metaphyseal and epiphyseal dysplasias.