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PubMed1977

Osteogenesis after bone and bone marrow transplantation. II. The initial cellular events following transplantation of decalcified allografts of cancellous bone.

An experimental study was done in rabbits to investigate the fate of allogeneic iliac cancellous bone, both non-decalcified and decalcified with hydrochloric acid, transplanted to a muscular site for up to 14 days. Some of the treated allografts were impregnated with autologous bone marrow cells, obtained from the femoral medulla by aspiration, and each was compared with allografts alone. Combined myelo-osseous grafts produced bone after 7 to 8 days implantation, as did marrow autografts alone. In addition non-decalcified implants stimulated the production of multinucleated giant cells. Three different types of wash solution were used but these did not inftical events in bone formation after transplantation occur less than 8 days after tho the clinical aspects of bone grafting.

Animals↗
PubMed1979

Bone densitometry using computed tomography. Part I: selective determination of trabecular bone density and other bone mineral parameters. Normal values in children and adults.

Gamma-ray computed tomography (gamma-ray CT), using a special purpose scanner, enables in-vivo quantitative analysis of bone mineralization. Trabecular bone density (TBD), the relative amount of compact bone (bone density, BD) and the total absorption (TA) for a cross-section of the radius are determined from measurements of local linear absorption coefficients. A preliminary study of normal children (n = 49) and adults (n = 34) indicated that TBD is independent of age and sex in the age range 4 to 40 years. DB remains constant throughout childhood but increases after puberty in both women and men. TA is higher for adults than for children, and also higher for men than for women. A correlation between TA and parameters relating to body size indicates a relationship between body weight and bone mass.

Adolescent↗
PubMed1977

The reversibility of disuse osteoporosis. Studies of bone density, bone formation, and cell proliferation in bone tissue.

One hind leg of 80 adult rats of the Sprague-Dawley strain was made osteoporotic by immobilization for 9 weeks. Osteoporosis was noted in both the femur and the tibia when the hydrated gross bone density and the bone surface areas were measured. No signs of reversibility were observed during 10 weeks after the period of immobilization. Tetracycline and DCAF labelling failed to show significant signs of increased bone formation during the 10 weeks after remobilization. At the moment of remobilization and for some weeks thereafter, there were signs of depressed mitotic activity in the bone cells when expressed as the 3H-thymidine/DNA ratio. The conclusion was that neither the cell-proliferation rate nor the cellular activity increases sufficiently for restitution of the disuse osteoporosis.

Animals↗
PubMed1977

The degree of bone mineralization in different parts of human skeleton estimated from bone phosphorus/hydroxyproline.

To evaluation the uniformity of the degree of mineralization in the skeleton the bone phosphorus/hydroxyproline ratio (bone P/Hypro) was determined in different localizations of ten human skeletons. Marked differences in bone P/Hypro were found between cortical bone and spongy bone. No difference was found between cortical bone from humerus, femur and cranium. But the mean value of these cortical bones was significantly higher than the mean value of the studied spongy bones. No significant correlation was found between the two bone types. Differences in bone P/Hypro were also found between different spongy bones. In pelvis the value did not differ between four spongy bone localizations but the mean value was significantly lower than for the other spongy bones (thoracal column, lumbal column and clavicle). Between these other spongy bones no difference was found in mean bone P/Hypro, and the mean of the pelvic bone localizations correlated significantly to the other spongy bones. The study demonstrates differences in the chemical composition of the human skeleton. A value of bone P/Hypro in the iliac crest can be used to estimation of bone P/Hypro in other spongy bones but not in cortical bones.

Adult↗
PubMed1977

Decalcified bone as a substrate for osteogenesis. An appraisal of the interrelation of bone and marrow in combined grafts.

This paper examines the fate of decalcified allografts (homografts) of iliac cancellous bone impregnated with autologous red marrow and implanted intermuscularly into the anterior abdominal wall of rabbits. In contrast to the findings of Urist and other workers that cortical bone decalcified with hydrochloric acid (HCl) and then freeze-dried is inductive to new bone formation in various heterotopic sites, evidence is presented that iliac bone decalcified by HCl and grafted alone to a muscular site is itself very weakly inductive to bone formation. However, when combined with autologous bone marrow the HCl-decalcified bone provides a better substrate for bone formation by marrow cells than does either undecalcified iliac bone, or iliac bone decalcified with ethylene-diamine-tetra-acetic acid. The freezing or freeze-drying of decalcified bone does not affect new bone formation when implanted alone or with autologous marrow. The differences between the cortical and cancellous bone as inductive substrates for osteogenesis are discussed and the interrelationship of bone and marrow in combined bone grafts are re-evaluated.

Animals↗
PubMed1976

Phosphotungstic acid-iron-haematoxylin staining method for osteoid, boundary bone and bone components in paraffin sections.

A new staining technique which stains osteoid and bone tissue differentially and also demonstrates boundary bone, pathological osteoid and the changes in ageing, pathological and dead bone matrix in decalcified paraffin or low-viscosity-nitrocellulose bone sections was developed. This phosphotungstic acid-iron-haematoxylin (PTAIH) method is based on pretreating the sections with phosphotungstic acid followed by an iron alum mordant and staining in haematoxylin with subsequent timed differentiation, at certain stages of which the features listed above appear. Van Gieson's picrofuchsin is then used as a counterstain. After standard differentiation osteoid appears red in sharp contrast with the black bone, young and woven bone, old and lamellar bone, and allows one to demonstrate changes in stainability of diseased osteoid and bone matrix, and dead bone. With the differentiation done individually and interrupted at certain stages it is possible to distinguish between various bone components depending on the amount and quality of their in vivo mineralisation. Comparison with controls showed that in this respect the method is more sensitive than the curremt staining techniques of undecalcified bone sections since it demonstrates not only unmineralised and fully mineralised tissues but also shows the poorly calcified, demineralised and ill-calcified bone components. The advantages of the method compared with those using undecalcified sections are its simplicity, suitability for fixed and decalcified material in any unspecialised histological laboratory and the fact that osteoid and other bone components can be studied in sections of unlimited size and in undisturbed relationship to their surrounding soft tissues.

Aging↗
PubMed1976

Bone resorption measurement with unusual bone markers: critical evaluation of the method in phosphorus-deficient and calcium-deficient growing rats.

An in vivo method to evaluate bone resorption in rats, by using unusual bone seekers not dependent on renal tubular transfer, is described and a critical evaluation of the method is made. In our experimental conditions, 85Sr and 177Lu are virtually exclusively localized in bone whereas 237Np remains unchanged in different soft organs, so that the concomitant use of these markers can be used for measuring bone resorption. If osteolysis occurs 21 days after the injection of these markers, under our experimental conditions, any increase in the urinary excretion of 177Lu and 237Np represents a rise in bone resorption, whereas an increase in Sr excretion reflects both and renal tubular events. According to our bone localization studies, the enhancement of Lu and Np excretion reflects primarily an increase in cortical bone resorption localized at the endosteal (Lu) and at the periosteal (Np) surfaces respectively. In addition, strontium is considered to be the marker of mineral resorption whereas Lu and Np, under our experimental conditions, would reflect the organic bone resorption. This method is tested in phosphorus-deficient rats and in calcium-deficient rats which exhibit disturbances of calcium metabolism at both the bone and kidney levels. In agreement with previous investigations, the use of these bone markers to evaluate osteolysis shows: (a) after a 1-week phosphorus deficiency, a slight increase in cortical bone resorption with a simultaneous fall in calcium and strontium renal tubular reabsorption, and (b) after a 1-week calcium deficiency, a high rise in cortical bone resorption with a simultaneous increase in the renal tubular reabsorption of calcium and strontium.

Animals↗
PubMed1979

Induction of new-bone formation in the host bed by human bone-tumor transplants in athymic nude mice.

UNLABELLED: Specimens of twelve osteosarcomas, five chondrosarcomas, one giant-cell tumor, and five extraskeletal soft-tissue sarcomas were transplanted into male athymic nude (nu/nu) mice. Survival of the transplant was determined by the volume-doubling time and the sex chromatin of the tumor cells obtained from two female patients. By these criteria and the similarity of the histological composition of the original tumor and the transplant, survival occurred in four of twelve osteosarcomas and four of five chondrosarcomas. Without any local infiltration of lymphocytes or plasma cells, or other evidence of cell-mediated immunity, the surviving tumors regressed by the fourth week after the operation. Transformed osteoblasts and osteoprogenitor cells were replaced by fibrous connective tissue or fibrogenic tumor-tissue cells. Osteocytes degenerated and disappeared from the lacunae. The one giant-cell tumor transplant survived, growing very slowly, but by the end of the first week after transplantation whorls of mononucleated cells appeared in sites previously occupied by multinucleated cells. Transplants of leiomyosarcoma, liposarcoma, and synovioma (one tumor of each) degenerated. One of two fibrosarcomas survived transplantation. The most striking reaction of the mouse host bed was to encompass six of twelve osteosarcomas and four of five chondrosarcomas in deposits of normal living cartilage, bone, and bone marrow. The incidence of new bone inducedy by living transplants was only slightly greater than by implants of freeze-dried killed osteosarcoma tissue. Not one of five extraskeletal sarcomas, living or dead, induced bone formation. These observations suggest that an osteoinductive agent is transmitted by some osteosarcomas and chondrosarcomas. This agent initiates differentiation of host mesenchymal cells into normal non-tumorous cartilage and bone, which later colonized by bone marrow. CLINICAL RELEVANCE: Our observations present experimental evidence of the origin of the envelope of normal non-tumorous bone that may surround tumorous bone. In 1926, Phemister recognized the clinical significane of this envelope as a pitfall in the differential diagnosis of malignant bone tumors, chondrosarcoma, myositis ossificans circumscripta, and other neoplasms. He emphasized the importance of examining the entire specimen for the distribution of deposits of tumorous and normal bone. The induction of normal bone formation in the host bed surrounding transplants of osteosarcomas and some chondrosarcomas (but not transplants of fibrosarcoma, liposarcoma, or leiomyosarcoma) is evidence of a specific tumor-cell characteristic. Thus, the bone inductive response is not an unspecific reaction to injury from expansion or of tumor growth but a biological response to tumor-cell products. Transplants of human malignant tumors growing in the thymus-deficient mouse can be treated by combinations of radiation, amputation, and new chemotherapeutic agents...

Adolescent↗
PubMed1978

Rationale for the use of bone scans in selected metastatic and primary bone tumors.

Since the introduction of bone scans in 1951, there have been many studies comparing biologic and physical characteristics of new bone-imaging agents and the results of scintigraphy and radiology in large numbers of patients. Relatively speaking, there have been fewer studies detailing the health benefits and financial cost associated with the use of skeletal scintigraphy. This review concerns these aspects in patients with malignancies of various sites and stages. About 2% of patients with stage I or II breast cancer have bone metastases at the time they first present, whereas nearly 28% of patients with stage III disease have bone metastases. A large percentage of patients with initially negative scans develop bone metastases during the first 3--4 yr; many of them develop them within the first 12--18 mo after initial diagnosis. For patients with lung cancer, the use of bone scans in staging their disease is somewhat controversial. Several studies indicate that the yield of positive bone scans may range from as low as 2% to as high as 35%. Data on the use of bone scans in staging prostatic cancer initially are similar to those in patients with breast cancer, that is, yields of 7% in patients with stage I or II disease and a yield of about 20% with stage III disease. Children with osteosarcoma or Ewing's sarcoma rarely have bone disease distant from the site of their primary bone lesion at presentation. However, a large percentage of them (30%--40% or so) develop bone metastases during the follow-up period. As in the case with patients with breast cancer, about half of these bone metastases are evident by 12--18 mo.

Bone Neoplasms↗