Comparative study of bone mineral density estimated by various methods of single- and dual-energy quantitative computed tomography: the capability of the four-equation four-unknown method.

A dual-energy (DE) quantitative computed tomography (QCT) method, the four-equation four-unknown method (DEQCT 4E-4U), was assessed and compared to single-energy (SE) QCT and standard DEQCT (two-line method). The results of this study indicate that bone mineral density (BMD) was more accurately estimated by the present method than by the SEQCT or standard DEQCT techniques on the basis of a phantom study when a large fat content was present. The results of both the phantom study and a human study also showed that the present method corrected for fat in estimating BMD in the presence of high-fat content. These findings suggest that use of this method for estimating BMD can provide useful information in studies assessing the metabolic state of bone. We propose that CT numbers estimated from excised vertebral bone marrow can serve as a soft-tissue correction for the present method.

Measurement of sulfidopeptide leukotrienes and their metabolism in human synovial fluid of patients with rheumatoid arthritis.

Leukotriene (LT)C4 in the synovial fluid of patients with osteoarthritis deformans (OA) and rheumatoid arthritis (RA) was measured by radioimmunoassay (RIA) after extraction with Sep-Pak C18 cartridge. The amounts of immunoreactive LTC4 (i-LTC4) in samples from patients with OA and RA were not significantly different, being 0.198 +/- 0.018 pmol/ml (n = 11) and 0.179 +/- 0.016 pmol/ml (n = 12), respectively. After separation by high performance liquid chromatography (HPLC) and measurement by RIA, the levels of other sulfidopeptide LTs, such as LTD4 and LTE4, in synovial fluid from patients with RA were found to be significantly higher than those in fluid from patients with OA. The leukocyte number in synovial fluids did not correlate with the i-LTC4 level. The metabolic activities of these synovial fluids were determined by incubating them with 3H-LTC4 and then separating sulfidopeptide LTs by HPLC. The conversion of LTC4 to LTD4 in synovial fluids of patients with OA and RA were similar, but the dipeptidase activity converting LTD4 to LTE4 was higher in fluid from patients with RA. It is suggested that a high level of LTE4 may contribute to exudation of synovial fluid, since LTE4 increases vascular permeability.

Spontaneous fractures of the hip in the elderly.

The authors found 41 patients with 42 fractures of the hip who had no distinct history of trauma in the total of 1,449 hip fractures treated. They were all women ranging in age from 64 to 91 years. Most of the fractures were of intracapsular type. Three extracapsular fractures, however, were found. Fractures were randomly selected with clear history of trauma, which were matched to the patients with no trauma for age, sex, and type of fracture as a control group. The grades of osteoporosis of the femoral neck, estimated with the Singh index, and of the spine, estimated with the spinal score, were noted statistically significantly higher in the patients than those in the control group. Most of spontaneous fractures of the hip in the elderly are considered similar phenomena to the compression fractures of the dorsolumbar spine.

[Pulmonary complications subsequent to fractured neck of the femur in the elderly].

Fracture of the neck of the femur (FNF) is a common disorder in the elderly. A total of 618 cases consisting of 117 males and 501 females, whose age was 65 years or more, were enrolled in a prospective study. A total of 45 cases among them revealed pulmonary complications. These were divided into the following three groups: Group 1 (4.7%) who had respiratory disease(s) or symptoms prior to the fracture; Group 2 (1.9%), diagnosed as having pulmonary thromboembolism (PTE). In Group 3 (0.6%), PTE was a possible diagnosis but it was not distinguished from pneumonia in precise. In the patients of group 2 and 3, respectively, the following respiratory symptoms were observed: dyspnea (31.3%), productive cough (25%), syncope (12.6%), chest pain (6.3%), tachycardia (46.7%), and tachypnea (50%). An abnormal chest roentgenogram was found 56.4% in both group 2 and 3. Seven patients in group 2 showed remarkable reduction of PaO2 on admission, however these all recovered within 7 days without any thrombolytic treatment. The prevalence of PTE caused by FNF in the elderly was close to that in younger cases, but the clinical symptoms were less in the former.

[Malignant tumors in a Japanese geriatric hospital].

We studied the cases of 909 patients with malignant tumors (497 men and 412 women) who were admitted to Tokyo Metropolitan Geriatric Hospital from April 1994 to July 1995. The mean age was 78.6 years (range: 60 to 103 years). The most common tumors were gastric cancer, colo-rectal cancer, and lung cancer. However, the most common tumors in those who died (n = 263) were gastric cancer, lung cancer, and liver cancer. In 425, abnormalities were found during routine health checks or incidental laboratory examinations, while the patients were asymptomatic. On the first admission, 23.4% were found distant metastases. The rate of complications with other diseases was 82.3%. About one third (31.2%) were informed of their situation, and 18.5% had not received any treatment for their malignancies. In 63%, performance status at the time of discharge was the same as that measured on admission or better.

Compositional changes of glycosaminoglycans of the human menisci with age and degenerative joint disease.

The compositional profiles of meniscal glycosaminoglycans (GAG) at different ages and in the presence of osteoarthritis were determined. The major components of meniscal GAG were chondroitin sulphates and dermatan sulphate. Other major elements were keratan sulphate and hyaluronic acid. Chondroitin sulphate-4 and -6 decreased with age. Dermatan sulphate content remained unchanged with age whereas keratan sulphate and hyaluronic acid increased. GAG compositional profiles of meniscus from osteoarthritis were similar to those of comparable age group. The results indicate that GAG compositional make-up of the meniscus changes with age. These changes may make it more susceptible to horizontal tears in the elderly.

Contact dermatitis sparing the eruption of herpes zoster and its periphery.

A 63-year-old male developed allergic contact dermatitis with antibiotic ointment applied to the skin eruptions of herpes zoster. From the result of patch test, fradiomycin sulfate contained in the ointment was identified as the contact sensitizing antigen. Strangely, this contact dermatitis was confined to the area surrounding the sores, sparing the lesions and their periphery. We postulated that a decrease in Langerhans cell activity in the herpes zoster lesions and their peripheral area was primarily responsible for this phenomenon, since an important role of Langerhans cells in host defence against herpes virus infection has recently been demonstrated.

Vitamin D3 metabolism in idiopathic osteonecrosis of femoral head.

Eighteen cases of idiopathic osteonecrosis of the femoral head were studied. Serum concentrations of 25(OH)D3, 24, 25(OH)2D3 and 1,25(OH)2D3 were 19.4 +/- 8.7 ng/ml, 1.04 +/- 0.44 ng/ml and 16.7 +/- 7.9 pg/ml (mean +/- SD) respectively. These values were significantly lower than those of control (26.5 +/- 15.5 ng/ml, 1.91 +/- 0.77 ng/ml and 26.9 +/- 13.7 pg/ml, respectively) (p less than 0.01). Abnormal values of serum calcium (Ca) were detected in two cases, inorganic phosphate (iP) in two cases and alkaline phosphatase (Al-Pase) in two others with no other abnormal values in blood biochemistry. Histological findings in nine cases of iliac bone were those of osteomalacia in five cases and those of osteoporosis in four cases. These results suggest the possibility of bone metabolism abnormalities due to abnormal vitamin D3 metabolism as a background of osteonecrosis of the femoral head.

Interleukin-4 stimulates pro-alpha 1(VI) collagen gene expression in cultured human osteoblast-like cells.

Interleukin-4 (IL-4) is a pleiotropic immunomodulatory cytokine produced mainly by T lymphocyte. It is known that many kinds of non-haematopoietic cells, as well as immune cells and haematopoietic cells, express IL-4 receptors. Recently, we found that IL-4 increased hydroxyproline and osteocalcin accumulation and caused mineralization in cultured human osteoblast-like cells. To clarify the mechanism of those effects of IL-4, we explored mRNAs whose expression levels were increased or decreased by IL-4 treatment using the method of differential display. As a result, expression of pro-alpha 1(VI) collagen gene in osteoblast-like cells proved to be substantially enhanced by IL-4 treatment. Considering that type VI collagen binds many kinds of extracellular matrices, type VI collagen probably mediates IL-4-dependent increase of accumulation of hydroxyproline and osteocalcin in cell layers of osteoblast-like cells.

The relation between osteoporosis of the spine and osteoarthritis of the knee. A study using dual energy X-ray absorptiometry and radiographs.

We investigated the relation between osteoporosis of the spine and osteoarthritis of the knee using dual energy X-ray absorptiometry of the lumbar spine to measure bone mineral density and radiographs of the knee in 82 randomly selected females (mean age 77.5 years). Radiographs of the knee were divided into a normal and severe group. The bone mineral density of the severe group was significantly more than that of the normal group.

Reversibility of alendronate-induced contraction in human osteoclast-like cells formed from bone marrow cells in culture.

Alendronate is a powerful therapeutic agent for the treatment of hypercalcemia in malignancy and osteoporosis and has recently been developed as a treatment for hypercalcemia of malignancy. In this study, time-lapse cinemicrography was used to investigate the effects of this agent on the morphology and the motility of human osteoclast-like multinucleated cells (MNCs) from human bone marrow. Alendronate at 10(-5)M induced contraction of the cells starting 7.5 h after its addition. Contraction was markedly induced immediately after alendronate removal. However, contraction almost disappeared 18h after removal, and osteoclast-like MNCs recovered their original sizes and shape. There was only partial recovery from contraction after alendronate treatment at 10(-4)M. In contrast, untreated control cells did not change their morphology after washing with culture medium. Motility analysis showed that osteoclast-like MNCs treated with 10(-5)M alendronate moved actively after washing, but at 10(-4)M the motility locus was very narrow. At 10(-4)M, the actin ring in the cells began to break down, beginning 6h after addition. The effects of alendronate on human osteoclast-like MNCs morphology and motility were reversible at 10(-5)M, suggesting that alendronate dose not cause any cellular damages in human osteoclasts up to 10(-5)M, which is an effective dose for bone resorption.

An aspect of metabolic bone disease with idiopathic osteonecrosis of the femoral head.

In spite of vast varieties of investigations on osteonecrosis, there is no report concerning the serum vitamin D metabolite concentrations and quantitative assessment of histological parameters of undecalcified section of bone. In this study, we examined the relations between biochemical and histological parameters in four patients with idiopathic osteonecrosis of the femoral heads. Serum 25-hydroxyvitamin D3 concentrations showed lower value within normal range. However, 1, 25-dihydroxyvitamin D3 and 24, 25-dihydroxyvitamin D3 concentrations were far below the normal value in all patients. Serum immunoreactive parathyroid hormone concentrations were within normal range. Histomorphometric parameters of iliac crest biopsy specimens were as follows. Relative osteoid volume, osteoid surface, and resorption surface were increased in all patients. Calcification front was decreased in all patients. Mean osteoid seam width was increased in two patients. These results suggest that microfractures created in such fragile trabeculae of femoral heads in our patients with deficiency of active vitamin D metabolites, will not be repaired well.

[Biochemical study of human articular cartilage and meniscus on aging and joint disease (author's transl)].

We studied biochemically the changes associated with aging and disease in the collagen of articular cartilages and menisci. Pepsin soluble and insoluble collagen were obtained by the method of Miller (1971) from the articular cartilages of seven healthy young and adult, six healthy aged subjects, and of six osteoarthritic and six rheumatoid arthritic patients. One portion of pathological cartilage was histologically examined to eliminate any possible contamination of the fibrous tissue and subchondral bone, and to classify the pathological findings. By the method of Miller, the pepsin soluble and insoluble collagen were also obtained from four adult and six aged menisci. Amino acid composition and carbohydrate contents were studied in insoluble collagen. The type of soluble collagen were analyzed with SDS disc electrophoresis. The amount of crosslinks in insoluble collagen was analyzed by the method of Masuda (1976) using automatic amino acid analyzer. The results obtained where shown as follow: 1) Solubility of collagen by pepsin decreased with aging on articular cartilages and menisci. In osteoarthritis and rheumatoid arthritis, the solubility of collagen by pepsin was different between the samples, and generally higher than that of collagen from the aged articular cartilages. 2) In respect to aldimine crosslinks of insoluble collagen, the dihydroxylysinonorleucine (DHLNL), hydroxylysinonorleucine (HLNL) and lysinonorleucine (LNL) increased with aging. DHLNL and HLNL were present in the nonreduced collagen in vitro. It was shown that the aldimine crosslinks had been already reduced in vivo. 3) The contents of carbohydrate of insoluble collagen from articular cartilage showed lower values than that of type II collagen as described previously. The hexosamine contents increased and those of uronic acid and hexose decreased with aging. In osteoarthritic and rheumatoid arthritic articular cartilages, the contents of uronic acid were lower than that of healthy aged group. The carbohydrate contents of menisci were similar to that of type I collagen. 4) concerning the type of collagen, healthy articular cartilages consisted of type II collagen. In collagen of aged cartilages and those of fibrillated and osteophytic cartilages in osteoarthritic and rheumatoid arthritic patients, the type II collagen were mixed with type I collagen ranging from 13.8% to 64.5%, although the analysis of articular cartilages in this study showed histological characteristics of hyaline cartilage. The type of soluble collagen in adult and aged menisci were composed of type I collagen in spite of aging.

[Comparison of treatments in senile osteoporosis: follow up for 12 months (author's transl)].

We randomly divided senile osteoporotic patients into 8 groups. Eleven patients of A-Group were treated daily with 900 mg of calcium and 50 mg of sodium fluoride and 50,000 units of vitamin D twice weekly. Fourteen patients of B-Group were treated daily with 900 mg of calcium and 50 mg of sodium fluoride. Twelve patients of C-Group were treated daily with 50 mg of sodium fluoride. Ten patients of D-Group were treated daily with 900 mg of calcium, 50 mg of sodium fluoride and 2 mg of estriol. Ten patients of E-Group were treated daily with 2 mg of estriol. Ten patients of F-Group were treated daily with 900 mg of calcium. Ten patients of G-Group were treated daily with 900 mg of calcium and 2 mg of estriol. The treatments were given for 12 months. Ten patients without treatment served as the non-treated control group. In each group, mineral contents were measured with Norland Bone Mineral Analyzer at the level of the distal third of the left radius and ulna before and after treatment. Mineral contents of ulnar bone in A-Group, of radial and ulnar bones in E-Group, F-Group, and G-Group increased with statistical significance after 12 months of the therapy. Mineral contents of radial and ulnar bones in C-Group and Nontreated Group decreased with statistical significance after 12 months. In laboratory examination, we observed no severe side-effect in our patients. But it was very interesting that the values of serum alkaline phosphatase in F-Group and G-Group decreased with statistical significance after 12 months of the therapies.

Biochemical features of pseudomembrane at the bone-cement interface of loosened total hip prostheses.

Biochemical features of pseudomembrane formed at the bone-cement interface of 13 failed total hip replacements were studied and histological examination of the pseudomembrane was conducted. The results of biochemical analyses revealed on average hydroxyproline, 86 micrograms/mg; water content, 57%; hexosamine, 12 micrograms/mg; glucosamine/galactosamine, 1.4%; and calcium, 2.1%. Approximately 78% of collagen was extracted with pepsin, whereas only 8 and 0.3% collagen were extracted with acetic acid and neutral salt, respectively. On further differential salting out of the extracted collagen, about 77% was type I collagen, 19% type III, and 2.6% type V. Unlike pseudoarthrosis of fracture, no type II collagen was identified. Overall biochemical features in the light of the histological appearance suggested that pseudomembrane resembles granulation tissue. Bone healing mechanisms at the bone-cement interface appear to differ from that of fracture healing.

Soft tissue collagen in congenital dislocation of the hip. Biochemical studies of the ligamentum teres of the femur and the hip joint capsule.

Collagens of the ligamentum teres of the femur and the hip joint capsule of 14 patients with congenital dislocation of the hip (CDH) were studied biochemically. Collagen was a major component of these tissues. Solubility of collagen was reversely related to age except in two cases. Collagen of both ligamentum teres of the femur and hip joint capsule was composed of type I, III and V collagens except in three cases. In these three cases with nevus or general joint laxity, two additional collagenous components were also found. The ratios of type III collagen to type I collagen were increased in CDH except in one case with short stature. These abnormalities of collagen metabolism could be the underlying cause of CDH and other clinical symptoms in these patients.