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Bone structure and function.

Bone is a complex, living, constantly changing tissue. The architecture and composition of cancellous and cortical bone allow the skeleton to perform its essential mechanical functions. The stiffer cortical bone responds more slowly to changes in loads while cancellous bone has a much larger surface area per unit volume and a greater rate of metabolic activity. Periosteum covers the external surface of bone and consists of two layers: an outer fibrous layer and an inner more cellular and vascular layer. The inner osteogenic layer or cambium layer can form new bone while the outer layer forms part of the insertions of tendons, ligaments and muscles. The cortical bone of diaphyses and metaphyses has a dual blood supply that allows loss of one source of circulation without adversely affecting the viability of the tissue. Many epiphyses, even in adults, depend only on a single source of blood supply, the penetrating epiphyseal vessels. For this reason epiphyseal bone may infarct more easily than metaphyseal or diaphyseal bone. The bone matrix has an organic component, primarily type I collagen, which gives it tensile strength and an inorganic component, primarily hydroxyapatite, which gives it stiffness to compression. Specialized populations of bone cells form, maintain and remodel this matrix. We recognize four types of bone cells based on their locations, morphology and functions: osteoprogenitor cells, osteoblasts, osteocytes and osteoclasts. Osteoblasts develop from undifferentiated cells while osteocytes form from osteoblasts. Osteoclasts have a separate stem cell line, blood-borne monocytes. Bone matrix apparently attracts these monocytes and stimulates their differentiation into osteoclasts. The processes of bone modeling and remodeling require osteoclastic resorption of bone matrix and deposition of a new matrix by osteoblasts. Modeling shapes and reshapes bones during growth and stops at skeletal maturity. Physiologic remodeling does not change bone shape and consists of bone resorption followed by bone deposition in approximately the same location. Since it continues throughout life it appears to be important for maintenance of the skeleton, but its exact function remains obscure. Adaptive remodeling is the response of the bone to altered loads and may alter the strength, density and shape of bone. In recent years understanding of the control of bone cell function has increased significantly. The study of electrical effects on bone formation has lead to new treatments of nonunions and delayed unions. Physicians have applied understanding of matrix-induced bone formation to reconstruction of skeletal defects.(ABSTRACT TRUNCATED AT 400 WORDS)

Bone Development↗

Interlocking intramedullary nailing in the treatment of tibial fractures. A report of 45 cases.

Forty-five tibial shaft fractures in 43 patients were treated with the Grosse-Kempf interlocking intramedullary nail. The material was highly selected because 49% of the fractures were due to high-energy trauma and 62% were located at the diaphyseal-metaphyseal junctions. The median time to full weight-bearing was 30 days, and 44 fractures healed by bridging callus in a median of 16 weeks. There was one nonunion, one deep, and one superficial infection. The results of the clinical and radiologic evaluations were excellent in 29 fractures, good in 13, fair in two, and poor in one. Interlocking intramedullary nailing proved to be efficient for comminuted, segmental, and unstable tibial fractures, especially in patients with multiple injuries. Compared with conventional intramedullary nailing, the locking procedure increases the stability at the fracture site and extends the indication for nailing to fractures in the proximal and distal diaphyseal-metaphyseal junctions.

Adolescent↗

Osteopetrosis: some unusual radiological features with a short review.

The radiological features of 27 cases of osteopetrosis were analysed retrospectively. The common features of generalized sclerosis of bones; with metaphyses showing characteristic widening, multiple transverse striations, cortical thickening and medullary calcifications as well as fractures, are seen in most cases. In addition to these changes, a number of rare features of osteopetrosis are seen, viz: medial and symmetrical metaphyseal cortical defects in the long bones (5 cases), excessive diaphyseal radiodense periosteal new bone formation (5 cases), bone-in-bone appearances (5 cases), and the presence of intracerebral and meningeal calcifications in 7 cases. The significance of these intracranial calcifications as a component of a particular autosomal recessive syndrome in which renal tubular acidosis and carbonic anhydrase II deficiency may co-exist, is discussed.

Bone and Bones↗

Effect of unilateral weight-bearing on pelvic limb development in broiler fowls: vascular studies.

Fifteen broiler fowls which habitually adopted a unilateral weight bearing stance were studied. In the majority of fowls the left pelvic limb was weight bearing and the right limb showed severe angular deformity. Dyschondroplasia occurred most frequently in the load-bearing limb. In the load-bearing limb the majority of lesions were in the femur and proximal tibiotarsus. In the non-load-bearing limb lesions most frequently occurred in the bone extremities of the distal tibiotarsus and proximal tarsometatarsus. Occluded epiphyseal vascular canals occurred in conjunction with physeal thickening at some dyschondroplastic sites. The majority of dyschondroplastic lesions contained elongated penetrating epiphyseal vessels and vessels derived from the perichondrial ring. These vessels were associated with chondrocyte hypertrophy and matrix calcification, which was considered to lead to the repair of the lesions. There was minimal calcification of cartilage at the base of the dyschondroplastic lesions and the underlying metaphyseal vessels were blunt ending. This suggested that a band of abnormal physeal cartilage was acting as a barrier to penetration by the metaphyseal vessels and so preventing subsequent endochondral ossification.

Animals↗

Morphological analysis and computer-aided, three dimensional reconstruction of chondrocytic columns in rabbit growth plates.

Proximal tibial growth plates of New Zealand white rabbits were serially sectioned in parasagittal and horizontal planes for three dimensional, light microscopic analysis of the chondrocytic columns. A total of 431 columns was analysed. Of these, 258 columns extended through the full height of the growth plate. The remaining columns were considerably shorter, being located either predominantly in the epiphyseal half of the growth plate (100) or in the metaphyseal half of the growth plate (73). The epiphyseal and metaphyseal columns were found in clusters in the plate. Some columns in all three groups had interruptions along their length, while others had duplications. Computer-aided, three dimensional graphic reconstructions were prepared of a selected group of columns. The reconstructions illustrated the variability in the morphology and the dimensions of the neighbouring chondrocytic columns. The observations suggest that chondrocytic columns in rabbit growth plates are replaced regularly and that the small cell zone may play an important role as the cellular source for column renewal.

Animals↗

[Histomorphometric analysis of the bones of rats on board the Kosmos 1667 biosatellite].

Bones of the rats flown on Cosmos-1667 were examined histologically and histomorphometrically. It was found that 7-day exposure to weightlessness led to osteoporosis in the spongy matter of proximal metaphyses of tibia and, although to a lesser extent, in the spongiosa of lumbar vertebrae whereas no signs of osteoporosis were seen in the spongy matter of iliac bones. Osteoporosis in the spongy matter of the above bones developed largely due to the inhibition of bone neoformation, which was indicated by a decrease in the number and activity of osteoblasts. Increased bone resorption (as shown by a greater number and activity of osteoclasts) was observed only in the spongy matter of tibial metaphyses. It is emphasized that a reduction of the number of highly active osteoblasts in spongy bones is one of the early signs of inhibition of bone neoformation and development of osteoporosis.

Animals↗

Immobilization-induced hypercalcemia and regional osteoporosis.

Immobilization hypercalcemia accompanied by unusual hormonal and bony changes complicated the Guillain-Barré syndrome in a 21-year-old woman. Metaphyseal rarefaction appeared in many sites and was severe in the lower limbs. A bone scan showed increased uptake of 99mTc methylene diphosphonate at these sites and throughout the axial skeleton. The literature on experimental metaphyseal rarefaction suggests that osteoclastic resorption and enhanced regional blood flow are associated with immobilization. Suppression of this osteoclastic component of the increased bone turnover, especially if it is widespread, was the rationale for treatment with calcitonin (CT). The patient also became amenorrheic, with low plasma gonadotropin and estrogen levels. Estrogen therapy coincided with a return of plasma calcium to normal.

Adult↗

Technetium-99m MDP scintigraphy. An insensitive tool for the detection of bone marrow metastases.

Seventy-nine cases with known carcinoma of the lung or breast who underwent both bone marrow aspiration and Tc-99m MDP bone scintigraphy were reviewed. The bone images were assessed for the presence of the pattern of bone marrow expansion which is visualized by diffuse increased metaphyseal activity, particularly evident at the knees, ankles, and elbows. This pattern was found to be an insensitive marker for the presence of marrow metastases (sensitivity 15%). The specificity of the finding was 86%. When diffuse increased metaphyseal activity is present on a Tc-99m MDP bone scan in a patient with malignant disease, the possibility of bone marrow metastases should be pursued by marrow aspiration and biopsy.

Biopsy, Needle↗

Massive allograft implantation following radical resection of high-grade tumors requiring adjuvant chemotherapy treatment.

Since 1976, the authors have performed a total of 36 resections of malignant tumors of the limbs with reconstruction of these by implantation of allografts. All allografts have been supplied by the University of Miami Tissue Bank. Following resection of the long-bone tumor and obtaining acceptable margins, the allograft was inserted to the limb defect with three different techniques: (1) in addition to a custom prosthesis as a hemi-joint reconstruction, i.e., a custom Neer prosthesis and proximal humerus allograft; (2) an osteoarticular graft to replace an articular surface resected with the metaphyseal-diaphyseal portion of the tumor; and (3) an intercalary diaphyseal-metaphyseal graft replacing the resected tumor but preserving the recipient articular surface. Of the 36 tumors, one was in Stage III disease. The remainder were Stage II A or B by the System of Enneking. All of these patients had adjuvant chemotherapy. The follow-up time was 24 months to 96 months. The resection of tumors in 36 patients and treatment with postoperative chemotherapy resulted in a mortality of eight out of 36 and one amputation due to recurrence. Satisfactory results were obtained in 19 of 36 patients. If the tumor failures (eight deaths) and the amputation are subtracted from this number, the success rate is 70% (19/27). Intercalary grafts were more successful than osteoarticular grafts. Chemotherapy was started one to two weeks postoperation for all but four patients to whom it was also given preoperation. These patients were in a Children's Cancer Study Group (CCSG) protocol for prospective study of the effects of preoperative chemotherapy. There was no apparent difference in the allograft success in these patients as compared to patients receiving only postoperative chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Osteochondrosis, dyschondroplasia, and osteomyelitis causing femoral head necrosis in turkeys.

Femoral head necrosis is a term that has been used, frequently inappropriately, to describe a variety of lesions in the head and proximal femur of poultry. In a survey of causes of lameness in a group of 18,000 tom turkeys, examination of femurs from lame 16-to-30-week-old heavy male turkeys with femoral head necrosis revealed that the lesions could be placed in one of three categories: degeneration of articular or growth plate cartilage and bone, with separation usually between the growth plate and metaphysial bone; avascular necrosis with sequestration and degeneration of an abnormal mass of prehypertrophying cartilage (dyschondroplastic cartilage), with spontaneous fracture and collapse of the femoral head or fracture through the metaphyses or neck of the femur; and osteomyelitis, with necrosis usually beneath the growth plate in the metaphyses. The second and third categories of lesion were frequently found in the proximal tibia as well, so the term long-bone necrosis would be a more suitable morphologic description than femoral head necrosis.

Animals↗

The fine structure of the proximal growth plate of the avian tibia.

The ultrastructure of the proximal tibial growth plate of the 7 weeks old chicken has been described. Little ultrastructural difference could be ascertained between growth plates examined from normal white leghorn and commercial broiler chickens. The growth plate may be divided into five zones: interstitial, proliferating, prehypertrophic, hypertrophic, and degenerating hypertrophic. These zones reflect a maturation of chondrocytes, beginning with a stage of high mitotic and cytoplasmic activity passing through a stage of active secretion of matrical components (prehypertrophic and hypertrophic) and ending with degeneration of the cells and calcification of the matrix. Mineralization of the matrix appears to be initiated within matrical dense bodies, as in the mammal. Single hydroxyapatite crystals are first encountered about 0.1 mm proximal (i.e. towards the knee) to the limit of metaphyseal blood vessel ingrowth, while dense calcification is observed 0.1 mm distal to the tips of these metaphyseal vessels. The diameter of microfibrillary collagen in the growth plate matrix ranges from approximately 9 nm in the proximal zones to 19 nm in the distal zones. Many of the fibrils in the distal zones have a more or less distinct periodicity. Other major elements of the growth plate matrix are the ruthenium red-stained syncytial aggregates of mucopolysaccharides which are probably derived from the granules within the large intracellular Golgi vesicles. These findings have led the author to conclude that, while light microscopy indicates that avian and mammalian growth plates have very different structures, electron microscopy finds many similarities, suggesting that the physiological control mechanisms in these two vertebrate classes have much in common.

Animals↗

[A study on experimental pyogenic osteomyelitis. 1. The preferential site of hematogenous osteomyelitis. 2. The role of foreign body in hematogenous infection (author's transl)].

The author undertook the experiments as described below in order to determine the preferential site of hematogenous osteomyelitis and possible effects of foreign bodies in the bone marrow on development of infection. I) In the first experiment, mice were inoculated with 10(7) cells of staphylococcus aureus intravenously into the tail vein and examined for the distribution and proliferation of the organisms in the bones, all over the body. It was found that the orgaisms in the blood stream were distributed to the bones all over the body almost evenly and that after prolonged observation, remarkable proliferation was noted in both femur and tibia. This bacteriological fact was supported by roentgenographic examination of all the bones. II) In the second experiment, inoculation of staphylococcus aureus into the tail vein was made after a foreign body (No. 5 sterile silk thread of 3 mm in lenght) had been inserted into the proximal metaphysis of a tibia of mice. The tibia of both legs was divided into 3 parts: proximal metaphysis, diaphysis and distal metaphysis. Observation were made for the distribution of organisms and state of proliferation in each of these three parts. In order to elucidate how the inserted foreign body promoted the establishment of infection, the group inserted with silk thread was compared with the control group (un-inserted group). The following results were obtained: 1. Although after 2 weeks of inoculation, the foreign body exerted no influences on the distribution and proliferation of organisms, but it was experimentally demonstrated to play a very important role for retention of organisms and maintenance of infection for a long period. 2. When the inoculum size was 10(6) to 10(7), the organisms were distributed evenly throughout the tibia. However, in the diaphysis the organisms tended to disappear, while in the metaphyseal area the organisms were easy to proliferate. It was also shown that at least 10(5) of organisms were needed for the establishment of infection and that the success or failure of establishment of infection is determined usually within 24 hours after inoculation of the organisms. As described above, from this study it was demonstrated that the femur and tibia were the preferential site of hematogenous osteomyelitis and that metaphyseal areas of the long bones were commonly affected. Once hematogenous invasion of organisms occurred, administration of antibiotics should be started as soon as possible, no later than 24 hours. According to our common experience, removal of foreign body is necessary for the complete cure of the injection.

Animals↗

A quantitative analysis of bone tissue formation in different regions of the spongiosa in the dog skeleton.

An investigation has been carried out on the relationship between the extent of bone tissue formation and the architecture of the "tubular" and "lamellar" components of the spongiosa within shaft bone ends, the anterior and posterior epiphyses and the intermediate portions of vertebral bodies in 3 dogs (aged 6 months, 2 and 3 years) treated for 3 consecutive days with tetracycline. The ratio of the extent of labelled surfaces to the sum of labelled plus unlabelled ones indicates the bone formation rate, referred to as osteogenic activity (OA). In the growing animal, a higher osteogenic activity is displayed by the "tubular" spongiosa, which lies peripherally in the metaphyses of shaft bones and consists of strong trabeculae nearly parallel to one another, and apparently arranged according to the distribution of mechanical stresses. In the adult dogs, the relatively higher osteogenic activity recorded in "lamellar" spongiosa appears to depend on a marked reduction in the osteogenic activity in the "tubular" spongiosa. In the vertebrae, osteogenic activity is higher in the central portion than in extremities solely during the period of growth in length: in the adult, the value of osteogenic activity was found to be practically uniform throughout the vertebral body. The "tubular" spongiosa, therefore, would be more actively involved in the remodelling of the metaphyses while the bone increases in length; the same would occur in the intermediate portion of the vertebral body. The reconstruction of the "lamellar" spongiosa, presumably less involved mechanically than the "tubular" spongiosa, would rather be an expression of bone mineral metabolism. A close relationship between spongiosa structure and osteogenic activity would occur at the ends of long bones and within the vertebral body.

Aging↗

The fine structure of the proximal growth plate and metaphysis of the avian tibia: endochondral osteogenesis.

The ultrastructure of endochondral osteogenesis from the proximal end of tibias of 7 weeks old normal White Leghorn and broiler chickens is described. Little, if any, ultrastructural differences exists between these two strains of birds. In the growth plate, proliferation of chondrocytes and their matriceal production is approximately matched by resorption. Erosion of the metaphyseal aspect of the growth plate is accomplished under two sets of circumstances: firstly, when mineralization of the cartilaginous matrix is so scanty as to be discernible only by electron microscopy, and secondly, when calcification is gross and easily appreciated by light microscopy. The former process appears to be accomplished in the main by perivascular mononuclear cells and the latter, to a great extent, by chondroclasts. It appears that metaphyseal blood vessels expand, by saccular protrusions, into pre-existing spaces or those created by cellular erosion. Cones or plates of calcified cartilage, which extend into the metaphysis, act as a template for initial deposition of bone. Osteoblasts recently surrounded by osteoid have adjacent to their plasmalemma a pericellular sheath which is composed of ill-defined clumps of amorphous material as well as some incompletely aggregated collagenous fibrils. Beyond this sheath collagenous fibrils and fibres, with distinct periodicities (ranging from 57 to 69 nm) are observed. Towards the diaphysis the range of the periodicity of fibres in osteoid narrows to 64-69 nm.

Animals↗

The effect of long-term low-dose diphosphonate treatment on rat bone.

Weaning, male rats were given ethane-1-hydroxy 1,1-diphosphonate (EHDP) or dichloromethylene diphosphonate (Cl2MDP) 0.5 mgP/kg/day for 140 days. Samples prepared after sacrifice were: (1) thin ground (30 micrometers) transverse tibial sections, (2) methacrylate-embedded 5 micrometers sections of the proximal tibial metaphysis, and (3) ultrathin calcified metaphyseal sections for electron microscopy. Cl2MDP reduced the diaphyseal medullary cavity, and EHDP increased the osteoid width. Both drugs increased endosteal bone apposition (possible secondarily to the impaired resorption) and, perhaps as a result, periosteal apposition was increased. Consequently, diaphyseal bone area was unchanged. Metaphyseal bone area was increased and osteoclast numbers reduced, in contrast to the increased osteoclast numbers reported previously in animal experiments with diphosphonates. Acid phosphatase activity within osteoclasts was markedly reduced with EDHP and unchanged with Cl2MDP. The ultrastructural changes in osteoclasts, i.e., a deficiency of ruffled borders, reduced numbers of cytoplasmic vacuoles and the presence of crystals between bone and the osteoclastic plasmalemma, were more marked with EHDP than Cl2MDP.

Animals↗

Short-term effects of vitamin D3 and 1,25-dihydroxyvitamin D3 on osteomalacia in uremic rats fed a low calcium-low-phosphorus diet.

The objectives of this study were to evaluate the effects of vitamin D(3) (D(3)) and 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) on uremic bone disease independent of their action on the intestine. The histomorphology of tibial metaphyses in uremic (5/6 nephrectomized [5/6 Nx]) rats fed a low-calcium-low-phosphorus (LCLP) diet was compared with sham-operated (SO) rats fed an LCLP diet and 5/6 Nx rats fed an LCLP diet and given 15,000 IU D(3) or 5 units (135 ng) 1,25-(OH)(2)D(3) daily for 7 days. A marked osteomalacia characterized by an increased percentage of active and inactive trabecular osteoid surface and thickened growth plates developed in proximal tibial metaphyses in 5/6 Nx rats given the placebo, compared with SO rats. These bone changes were associated with relative hypophosphatemia, hypophosphaturia, and hypercalciuria in 5/6 Nx rats. In 5/6 Nx rats treated with D(3) or 1,25-(OH)(2)D(3) the growth plates had undergone mineralization and vascular invasion and were markedly reduced in thickness. Other parameters of osteomalacia in trabecular bone were not different from 5/6 Nx rats given the placebo. There was a significant decrease in osteoclasts per millimeter of trabecular surface perimeter in D(3)- and 1,25-(OH)(2)D(3)-treated rats. These bone changes were associated with hypercalcemia, hyperphosphatemia, and hyperphosphaturia, compared with 5/6 Nx rats given the placebo. It was concluded that in uremic rats fed the LCLP diet, shortterm treatment with either pharmacologic levels of D(3) or 1,25-(OH)(2)D(3) corrected only lesions in the growth plate. Osteoid seams were not reduced in treated rats, although the serum calcium-phosphorus product was elevated. The 5/6 Nx rat fed the LCLP diet appears to be a useful model for the rapid induction of uremic osteomalacia in adult animals.

Animals↗

Formation and resorption of bone induced by demineralized bone matrix implants in rats.

Demineralized bone matrix was implanted in the abdominal wall of growing rats. 45Ca and 3H-proline were injected 21 days after implantation, and groups of animals were killed at 30 minutes to 16 days. Implants, tibial metaphyses and diaphyses, and incisor teeth were assayed for ash weights and isotope content. The net increase in mineral content was largest in the early phase of bone formation. Three weeks after implantation, the mineral accretion was approximately 10% of tibial metaphyses, or 0.06 mg ash per milligram implanted bone matrix. In both these tissues, the net increase in ash weight was only one-fourth of the accretion because of the high rate of resorption.

Animals↗

Experimental rickets in broilers: gross, microscopic, and radiographic lesions. II. Calcium deficiency.

Day-old broiler chicks were fed a calcium-deficient diet for 30 days. Gross, microscopic, and radiographic examinations of the proximal tibiotarsus were done at 2, 3, and 4 weeks of age. In 2-week-old chicks, the growth-plate proliferating-prehypertrophied zone (P-PHZ) was variably lengthened and disorganized, cartilage columns of the degenerating hypertrophied zone and metaphyseal primary spongiosa were shortened, and bone spicules of the secondary spongiosa were bordered by increased osteoid. In 3-week-old chicks, lesions were either similar or more pronounced, with the additional finding of metaphyseal peritrabecular fibrosis. In 4-week-old chicks, the P-PHZ decreased in relative length, osteoid seams and fibrous connective tissue were less prominent, and tibial dyschondroplasia-like lesions were present. Results demonstrated that dietary calcium deficiency produced rachitic lesions, that the lesions were very different from those of phosphorus deficiency or calcium excess, and that the lesions were variable over time.

Aging↗