Vincent J. Vigorita

The healing of segmental bone defects induced by demineralized bone matrix. A radiographic and biomechanical study.

UNLABELLED We studied the effect of demineralized bone matrix on the repair of large femoral diaphyseal defects in a rat model by clinical, radiographic, and biomechanical methods. A standard procedure was first developed to create segmental defects that did not heal and in which non-union developed consistently. The effect of demineralized bone matrix on repair was then assessed by physical examination, serial radiographs, and biomechanical studies to determine deformation to failure, stiffness, torsional strength, and energy absorption. By twelve weeks, the defects that had been treated with demineralized bone matrix showed satisfactory repair and remodeling in most animals based on clinical and radiographic evaluation. The biomechanical studies demonstrated that the bone induced by demineralized bone matrix had an energy-absorption capacity and stiffness equal to those of intact rat femoral bone. The bone induced by demineralized bone matrix achieved 35 per cent of the torsional strength of normal bone and an increased capacity to deform under load. These biomechanical properties are similar to those observed in the early stages of normal fracture repair. CLINICAL RELEVANCE An effective, readily available alternative to autologous bone-graft material would have a variety of clinical uses in orthopaedic surgery, such as augmenting fusions, aiding in the repair of high-risk fractures, and filling or bridging bone defects. Demineralized bone matrix may provide an important tool for these purposes by inducing bone that has the mechanical properties of fracture callus. This would reduce the morbidity associated with harvesting autologous bone and have an advantage over allografts or synthetic biomaterials that require incorporation by the host before they can support mechanical loads.

Chemical, microscopic, and ultrastructural characterization of the mineral deposits in tumoral calcinosis.

The presence of hydroxyapatite has been determined based on ultrastructure, X-ray diffraction, electron diffraction, and chemical analysis, and confirmed by microprobe analysis in multiple deposits surgically excised from four unrelated patients with tumoral calcinosis. The chemical composition of each of the mineralized deposits resembled bone, rather than dermis, in mineral, uronic acid, total lipid, and complexed acidic phospholipid composition. No collagen abnormalities were detected. However, all of these deposits differed from normal bone mineral, being heavily mineralized and containing larger, more perfect hydroxyapatite crystals. Ultrastructurally, the crystals were both extracellular and within mononuclear cells in close proximity to dilated rough endoplasmic reticulum.

Histochemical demonstration of iron but not aluminum in a case of dialysis-associated osteomalacia

A patient undergoing hemodialysis is described in whom osteomalacia developed despite protracted treatment with calcitriol. Appropriately stained biopsy sections exhibited iron at all marrow-osteoid interfaces and a small fraction of trabecular mineralization fronts. Aluminum, the metal usually associated with osteomalacia in patients undergoing hemodialysis, was not histochemically demonstrable, even though spectrophotometrically measured bone aluminum content was substantial. These observations suggest two interpretations: iron may have caused osteomalacia through effects on bone cells and at mineralization fronts; alternatively, aluminum may have caused osteomalacia while remaining histochemically undetectable. It is possible that both metals exerted toxic effects simultaneously.

Acidosis-induced osteomalacia: Metabolic studies and skeletal histomorphometry

The pathogenesis of osteomalacia was investigated in three patients with chronic metabolic acidosis. Serum levels of parathyroid hormone and vitamin D metabolites were measured, and bone biopsy specimens were analyzed after double tetracycline labeling. Parathyroid hormone concentrations were normal in patients 1 and 3 and slightly elevated in patient 2. Vitamin D metabolism was undisturbed. Static indicators of bone remodeling substantiated the diagnosis of osteomalacia in each case. In patient 1 fluorescent microscopy revealed no evidence of tetracycline uptake. In patients 2 and 3 active mineralization was evident at all osteoid seams, but because double labels were rare, the mineral apposition rate appears to have been substantially reduced in most bone-forming units. Our results indicate that acidosis-induced osteomalacia, unlike that due to vitamin D deficiency, may be associated with mineral deposition at every possible site. Nevertheless, like other causes of osteomalacia, metabolic acidosis prevents mineral apposition at a normal rate even if mineral deposition is ubiquitous. We suggest that titration of newly deposited phosphate causes the observed impairment of mineral apposition and ultimately leads to osteomalacia.

Intraosseous xanthoma associated with hyperlipoproteinemia. A case report.

Intraosseous xanthoma associated with hyperlipoproteinemia, a rare disorder, was observed in the entire distal femur of a 52-year-old man. Initial radiographs suggested a primary bone neoplasm; however, an open biopsy established a diagnosis of intraosseous xanthoma. Histologically, the lesion was characterized by replacement of normal bone and marrow with xanthoma cells and extracellular cholesterol clefts. The hyperlipidemia was classified as Type III hyperlipoproteinemia and was successfully controlled by dietary lipid restriction alone. The disability was effectively treated and ambulation was possible with the aid of a cane.

Neovascularity in chronic posterior tibial tendon insufficiency.

Insufficient posterior tibial tendons in 28 specimens from patients with clinical Stage II or III disease were examined to clarify the etiology of adult-acquired flatfoot deformity. Hematoxylin and eosin and Masson trichrome-stained sections of formalin-fixed tissue were viewed in plain and polarized light. We performed a qualitative analysis for abnormalities in collagen orientation, degree of vascularization, tenocyte cellularity, mucinous change, and chondroid metaplasia. Tendons were divided into three zones: tenosynovial lining cell layer, subtenosynovial lining cell layer, and tendon proper. All tendons showed neovascular infiltration causing collagen fibril disruption; 50% of specimens had diffuse involvement. Increased mucin content and chondroid metaplasia occurred in 28% and 36% of specimens, respectively. The tenosynovial lining cell layer showed hyperplasia in 28% of specimens. The subtenosynovial lining cell layer showed thickening and neovascularization in 79% of specimens, which appeared to be the source for the diffuse neovascular infiltrative process. There is little histopathologic evidence to support an inflammatory etiology to the posterior tibial tendons in acquired-adult flatfoot deformity. Neoangiogenesis, the prominent histologic finding, is consistent with an obscure insult. We postulate that overuse, tension, or stretching may activate the tenosynovial lining cells and incite angiogenesis.

Ultrastructural features of giant cell tumors in Paget's disease.

Giant cell tumor is a rare complication of Paget’s disease. This association is especially notable in patients originating from Avellino, Italy. Many types of evidence point to a viral etiology for Paget’s disease and giant cell tumors arising in it. Three patients who had giant cell tumors and Paget’s disease were studied. Two of the patients have a connection to Avellino (one was born in Avellino, and one descended from natives of Avellino). Distinctive light microscopic and ultrastructural features common in these three patients were identified. In all three patients, the giant cell tumors had peculiar irregular aggregates of microfilaments of uncertain genesis. The possibility that these reflect viral infection is discussed.

Neural anatomy of the transverse carpal ligament.

Carpal tunnel syndrome is one of the most commonly diagnosed disorders of the upper extremity. The etiology of the neuropathy is known to be associated with many disorders, with the etiology of carpal tunnel syndrome mainly attributable to ischemia of the median nerve. The purpose of this study was to determine the presence of neural elements within the transverse carpal ligament. Fourteen transverse carpal ligaments were harvested from seven male and seven female fresh frozen cadavers with an average age of 76 years. The tissues were stained with S-100 using a standard immunoperoxidase technique used to localize neural tissue. The transverse carpal ligament consisted of interwoven bundles of fibrous connective tissue. It was found to have an intraligamentous and extraligamentous neural network consisting mostly of free nerve endings and pacinian corpuscles. Ruffini’s corpuscles were not identified. This study showed that there is neural innervation to the transverse carpal ligament. Pacinian corpuscles have been shown to be mechanoreceptors which respond to changes in joint position, whereas free nerve endings have been identified as nociceptors. Neural innervation were present in the transverse carpal ligament, and the nociceptive information relayed by these neural elements may contribute to the pain associated with carpal tunnel syndrome. In addition to being a mechanical wrist stabilizer, the transverse carpal ligament also may play a role in proprioception of the wrist.

Differences between lactase deficient and non-lactase deficient women with spinal osteoporosis

Both osteoporosis and lactase deficiency are seen commonly in the United States. Since the latter may lead to avoidance of calcium sources and may exacerbate the bone disease in populations at risk, we studied lactose tolerance and histomorphometrically analyzed undecalcified transiliac bone biopsies in a consecutive group of postmenopausal women with the osteoporotic spinal compression fracture syndrome. Oral lactose tolerance tests prior to the biopsy clearly separated two groups. Sixty-five percent had abnormal test results. The bone biopsies in the lactase deficient group showed more osteoid volume and osteoid seam widths on examined trabecular bone. Analysis of tetracycline-labeled bone revealed significant increases in both single, double, combined single and double tetracycline labels, and the percent osteoid labeled with tetracycline. There was no difference in the calcification rates. These findings indicate different mineralization activity in lactase deficient patients, possibly reflecting their lower dietary calcium intake.

Hyperphosphatasemia in an adult. Clinical, roentgenographic, and histomorphometric findings and comparison to classical Paget's disease.

A 54-year-old man with short stature, diffuse skeletal abnormalities, and elevated alkaline phosphatase was evaluated by bone biopsy with undecalcified sections and morphometry analysis. Microscopically the bone changes were identical to those of classic Pagets disease. Histomorphometric analysis of bone demonstrated a high remodeling activity with increased mineralization rate similar to Pagets disease. However, the early age at onset and severity suggest that this man suffers from hyperphosphatasemia, a different and distinct condition.