Michael R. Sarkar

Correlation of bone mineral density with strength and microstructural parameters of cortical bone in vitro

The aim of this study was to evaluate the influence of microstructural parameters, such as porosity and osteon dimensions, on strength. Therefore, the predictive value of bone mineral density (BMD) measured by quantitative computed tomography (QCT) for intracortical porosity and other microstructural parameters, as well as for strength of cortical bone biopsies, was investigated. Femoral cortical bone specimens from the middiaphysis of 23 patients were harvested during total hip replacement while drilling a hole (dia. 4.5 mm) for the relief of the intramedullary pressure. In vitro structural parameters assessed in histological sections as well as BMD determined by quantitative computed tomography were correlated with yield stress, and elastic modulus assessed by a compression test of the same specimens. Significant correlations were found between BMD and all mechanical parameters (elastic modulus: r = 0.69, p < 0.005; yield stress: r = 0.64, p < 0.005). Significant correlations between most structural parameters assessed by histology and yield stress were discovered. Structural parameters related to pore dimensions revealed higher correlation coefficients with yield stress (r = -0.69 for average pore diameter and r = -0.62 for fraction of porous structures, p < 0.005) than parameters related to osteons (r = 0.60 for osteon density and average osteonal area, p < 0.005), whereas elastic modulus was predicted equally well by both types of parameters. Significant correlations were found between BMD and parameters related to porous structures (r = 0.85 for porosity, 0.80 for average pore area, and r = 0.79 for average pore diameter in polynomial regression, p < 0.005). Histologically assessed porosity correlated significantly with parameters describing porous structures and haversian canal dimensions. Our results indicate a relevance of osteon density and fraction of osteonal structures for the mechanical parameters of cortical bone. We consider the measurement of BMD by quantitative computed tomography to be helpful for the estimation of bone strength as well as for the prediction of intracortical porosity and parameters related to porous structures of cortical bone.

First histological observations on the incorporation of a novel calcium phosphate bone substitute material in human cancellous bone

Calcium phosphates are frequently used as bone substitute materials because of their similarity to the mineral phase of bone, absence of antigenicity, and excellent osteoconductivity. However, in most currently available mineral substitutes, resorption occurs slowly if at all. In contrast, calcium phosphate cements have shown rapid resorption and remodeling in animal studies. In two prospective studies, a novel amorphous calcium phosphate cement (Biobon) was implanted in human patients for the first time. After 2-12 months, ten biopsies were obtained from nine individuals during secondary surgical interventions, for example, for implant removal. In all specimens, partial replacement of the material by new bone was observed, while residues of the cement were still visible. Undecalcified sections revealed extensive bone formation in immediate contact to the cement without fibrous interface. Polynucleated cells and superficial lacunae were indicative of resorptive activity, but inflammatory tissue response was absent. The new bone displayed regular trabecular and osteonal patterns. The histologic findings are in accordance with the excellent biocompatibility observed in the clinical follow-up. Though still incomplete, the resorbability of this cement appears superior to sintered calcium phosphates in these biopsy specimens. Presumably this is due to its amorphous crystalline structure. Biobon merits further studies as a promising substance for bone defect reconstruction in non-stress-bearing areas.

Predictive value of bone mineral density and morphology determined by peripheral quantitative computed tomography for cancellous bone strength of the proximal femur.

Peripheral quantitative computed tomography (pQCT) is an established diagnostic method for assessment of bone mineral density in the diagnosis of osteoporosis. However, the capacity of structural parameters of cancellous bone measured by high-resolution computed tomography remains to be explored. In 33 patients, bone mineral density (BMD) of the proximal femur was measured in vitro by pQCT using cylindrical biopsies from the intertrochanteric region harvested before the implantation of an artificial hip joint. By digital image analysis of CT scans, parameters derived from histomorphometry describing the microarchitecture of cancellous bone were measured. The biopsies were also loaded to failure by an uniaxial compression test to determine the biomechanical parameters, Youngs modulus, strength, and maximum energy absorption (E(max)). Strong correlations were found for BMD vs. mechanical parameters (r = 0.73 for Youngs modulus, r = 0.82 for strength, and r = 0.79 for E(max); p < 0.001, n = 29). The morphological parameters, bone volume per trabecular volume (BV/TV), apparent trabecular thickness (app.Tb.Th), apparent trabecular separation (app.Tb.Sp), and trabecular number (Tb.N), correlated significantly with all mechanical parameters. The combination of morphological parameters with BMD in a multivariate regression model led to an overall, but only moderate, increase in R(2) in all cases. Our data confirm the high predictive value of BMD for the mechanical competence of cancellous bone of the intertrochanteric region. However, quantification of cancellous bone structure by image analysis of CT scans may provide additional qualitative information for the analysis of bone strength.

Buruli Ulcer: A Systemic Disease

We studied a 4-year-old boy from Angola who presented with 2 cutaneous ulcerations of the right hip and osteomyelitis of the left knee and right ankle. Mycobacterium ulcerans disease was confirmed by direct smear examination and by polymerase chain reaction. The patient was treated with antimycobacterial drugs, repeated surgical debridement, skin grafting, and daily hyperbaric oxygenation. Despite significant improvement of the local lesions in response to hyperbaric oxygenation, swelling of the right knee, without associated skin lesions, was noted. Radiological evaluation and open biopsy revealed extensive metaphyseal osteomyelitis of the right distal femur. A 99technetium bone scan revealed an additional focus in the diaphysis of the left humerus, without soft-tissue involvement. This case documents, for the first time (to our knowledge), the systemic spread of M. ulcerans, with subsequent multifocal osteomyelitis and secondary involvement of soft tissues and supports the hypothesis that low tissue oxygen levels promote hematogenous spread of M. ulcerans. Sickle cell anemia, with associated microthrombosis and microinfarction, may have contributed to tissue hypoxia.

Prediction of strength of cortical bone in vitro by microcomputed tomography

OBJECTIVE The aim of this study was to evaluate the predictive value of bone mineral density and intracortical porosity measured by microcomputed tomography for the strength of cortical bone biopsies. DESIGN Experimental study comparing the predictive value of bone mineral density and of intracortical porosity determined in vitro by microcomputed tomography for the mechanical properties of cortical bone cylinders. BACKGROUND The assessment of cortical bone strength might be relevant for the prediction of fracture risk or the choice of suitable therapy strategies in orthopaedic surgery. The predictive value of cortical density for the mechanical properties is discussed controversially. The relevance of intracortical porosity measured by histomorphometry has been established, but the predictive value of porosity determined by microcomputed tomography remains to be explored. METHODS Femoral cortical bone specimens from the mid diaphysis of 24 patients were harvested during total hip replacement procedure at the location, where a diaphyseal hole (diameter 4.5 mm) was drilled in order to reduce the intramedullary pressure. In vitro intracortical porosity and bone mineral density measurements by microcomputed tomography were compared with strength and elastic modulus assessed by a compression test transverse to the Haversian systems of the same specimens. RESULTS Significant negative correlations were found between porosity measured by microcomputed tomography scans and yield stress, stiffness and elastic modulus (P<0.001), however, the positive correlations between bone mineral density and mechanical parameters were stronger (P<0.0001). The mechanical parameter best predicted by mineral density as well as by porosity was yield stress (r=0.72,P<0.0001;r=-0.64,P<0.001). CONCLUSIONS Bone mineral density determined by microcomputed tomography imaging in vitro may be a potent method to predict mechanical properties of cortical bone non-destructively. The application in vivo remains to be explored.

Predictive value of Singh index and bone mineral density measured by quantitative computed tomography in determining the local cancellous bone quality of the proximal femur

OBJECTIVE The purpose of this study was to assess the predictive value of the Singh index as well as quantitative computed tomography for the in vitro local mechanical competence of the cancellous bone of the proximal femur. DESIGN An experimental study examining the relation between mechanical properties and bone mineral density of the femoral neck determined in vitro and the clinical estimated Singh index on X-rays. BACKGROUND Evaluation of the predictive value of the Singh index, an inexpensive and simple technique for the mechanical properties of the cancellous bone of the proximal femur. METHODS The bone quality of the proximal femur of 34 patients undergoing total hip replacement was estimated by roentgenography using the Singh index. Bone mineral density was quantified by quantitative computed tomography using cylindrical cancellous bone biopsies harvested during the total hip replacement procedure by a new biopsy method. The mechanical properties of the bone specimens (Youngs modulus, strength and maximum energy absorption E(max)) were measured by mechanical testing of the bone biopsies. RESULTS A strong correlation of the Singh index versus material properties of cancellous bone was noted (r=0.66 for Youngs modulus, r=0.73 for strength and r=0.69 for E(max), P<0.0001). The correlations of bone mineral density measured by quantitative computed tomography versus Youngs modulus, strength and energy absorption E(max) were significant. Strength was predicted best (r=0.82; P<0.0001), followed by E(max) (r=0.79; P<0.0001) and Youngs Modulus (r=0.73; P<0.0001). CONCLUSIONS We conclude, that assessment of bone mineral density by quantitative computed tomography is a reliable and precise method for the estimation of cancellous bone material properties. The Singh index provides a rough estimate for the mechanical competence of the proximal femur. It is inexpensive, simply to assess and can in some cases replace the measurement of bone mineral density, notably in cases of marked decrease in bone density.

Molecular profiling of chordoma

The molecular basis of chordoma is still poorly understood, particularly with respect to differentially expressed genes involved in the primary origin of chordoma. In this study, therefore, we compared the transcriptional expression profile of one sacral chordoma recurrence, two chordoma cell lines (U-CH1 and U-CH2) and one chondrosarcoma cell line (U-CS2) with vertebral disc using a high-density oligonucleotide array. The expression of 65 genes whose mRNA levels differed significantly (p<0.001; ≥6-fold change) between chordoma and control (vertebral disc) was identified. Genes with increased expression in chordoma compared to control and chondrosarcoma were most frequently located on chromosomes 2 (11%), 5 (8%), 1 and 7 (each 6%), whereas interphase cytogenetics of 33 chordomas demonstrated gains of chromosomal material most prevalent on 7q (42%), 12q (21%), 17q (21%), 20q (27%) and 22q (21%). The microarray data were confirmed for selected genes by quantitative polymerase chain reaction analysis. As in other studies, we showed the expression of brachyury. We demonstrate the expression of new potential candidates for chordoma tumorigenesis, such as CD24, ECRG4, RARRES2, IGFBP2, RAP1, HAI2, RAB38, osteopontin, GalNAc-T3, VAMP8 and others. Thus, we identified and validated a set of interesting candidate genes whose differential expression likely plays a role in chordoma.

Acute Total Hip Replacement for Displaced Acetabular Fractures in Older Patients

Background:Primary total hip arthroplasty (THA) has been suggested for old patients with acetabular fractures, because it permits immediate full weight bearing and precludes secondary surgery for posttraumatic osteoarthritis.Patients and Methods:The authors retrospectively analyze the outcome after 35 primary THAs performed between 1982 and 2001 focusing on complications, functional impairment and pain.Results:19 patients were available for a follow-up after a median of 6 years. Seven patients had died and nine were lost to follow-up. Among those available for follow-up, four were severely handicapped or required regular analgesic medication. By contrast, four were able to work regular hours or to engage in sports activities. Eight patients had undergone various revision procedures.Conclusion:Primary THA is an option for the treatment of acetabular fractures in aged or chronically ill patients as well as for individuals with concomitant osteoarthritis at the time of fracture. However, complications are not infrequent and a solid buttress achieved, e. g., by a roof reinforcement ring (“hemispherical plate”) is considered crucial for a successful outcome.

Defect Reconstruction in Articular Calcaneus Fractures with a Novel Calcium Phosphate Cement

AbstractBackground: Major osseous defects in trauma or tumor patients require surgical reconstruction. While transplantation of autogenous or allogenous bone is still regarded as the standard, a multitude of alternative substitute materials has been developed in the recent years. Currently, the majority of commercially available products is based on calcium phospate minerals which are known to be osteoconductive, but in which resorption occurs slowly, if at all. A new class of calcium phosphate cements has recently been introduced that may offer better resorbability due to their nanocrystalline structure. Patients and Methods: In a prospective study of eleven patients with twelve joint depression calcaneal fractures requiring open reduction and internal stabilization, the subchondral defects were filled with a novel nanocrystalline calcium phosphate cement (Biobon®). Nine patients with ten fractures underwent a 1-year clinical and radiologic follow-up. Results: The postoperative course was uneventful except for one postoperative infection. On follow-up X-rays, the contours of the cement material became blurred and its size decreased. Biopsies taken after 6–8 months during plate removal demonstrated residual cement with intense osseointegration. Signs of inflammatory tissue response were absent, and part of the material had been replaced by new bone. Conclusions: The substitute material investigated in this study has a high biocompatibility and may represent an interesting alternative to bone grafts. Compared to sintered calcium phosphates, the resorbability of the new cement appears superior due to its nanocrystalline structure. The low compressive strength, however, does not permit early weight bearing and requires additional stabilization with osteosynthetic implants.

Bone Substitution and Augmentation in Trauma Surgery with a Resorbable Calcium Phosphate Bone Cement

AbstractBackground and Purpose:Synthetically manufactured bone substitute materials are widely used to fill cancellous bone defects in fracture treatment. By using these materials, complications occurring with the harvesting of autologous bone such as inflammation, hemorrhage and pain are prevented. Ideally, after osteointegration, the bone substitute resorbs, and complete restoration of bone architecture is achieved. Until now, clinical experience is limited to non-fully resorbable calcium phosphates, e. g., hydroxyapatite. Previous studies have revealed a fully resorbable pure calcium phosphate, which is applied in a paste form as a bone implant and results in complete resorption and biocompatibility. The purpose of this prospective, uncontrolled clinical study was to investigate the safety and performance of this new resorbable bone substitute material.Patients and Methods:In 107 patients, bone defects were filled with 1.0–27.5 g (median 5.45 g) of the bone substitute material. From 15 patients, biopsy samples for histological examination could be taken during secondary surgery, mostly when implants for osteosynthesis had to be removed.Results:On clinical, radiologic and histological examination, the bone substitute material studied appeared safe and efficient for filling bone defects in fracture treatment, showing resorption and osseous integration during remodeling of bone. No clinical signs of allergic reactions or inflammation did occur.Conclusion:When using calcium phosphate bone cement, a second surgical procedure to harvest autologous bone is not necessary and complications at the donor site are avoided.