Itsuo Yamamoto

Human calcitonin gene-related peptide possesses weak inhibitory potency of bone resorption in vitro

SummarySynthetic human calcitonin gene-related peptide (CGRP) was examined for the action on the bonein vitro. Human CGRP inhibited bone resorption stimulated by both human parathyroid hormone and basal. The mode of inhibitory action of human CGRP seemed to be similar to that of calcitonin and the relative potency of human CGRP to inhibit bone resorption is one five-hundredth of that of human calcitonin. Thus, a novel pharmacological action of CGRP was demonstrated.

Osteoclast-mediated osteolysis in bone metastasis from renal cell carcinoma

Osteolytic characteristics of bone metastasis from renal cell carcinoma were morphologically and biochemically investigated. First, undecalcified ground sections of bone metastases were made from four patients with renal cell carcinoma. Second, renal cell carcinoma cell line (RCC‐K1) was established from one of the four patients, and its effect on bone resorption in vitro was examined. Marked proliferation and activation of osteoclasts around the tumor cells was histologically demonstrated. Conditioned medium from the RCC‐K1 cells contained potent bone‐resorbing activity in vitro. The activity was reduced to basal level by calcitonin, but was not blocked by indomethacin. The activity was lost after dialysis (MW cutoff 3500), while it was retained after 2 weeks of storage. Levels of prostaglandin E2 and 1,25‐dihydroxyvitamin D of the RCC‐K1‐conditioned medium were insufficient to cause bone resorption in vitro. The conditioned medium did not stimulate cAMP accumulation in rat osteoblastic cells. These results suggest that renal cell carcinoma causes bone destruction through the stimulation of osteoclasts by locally secreting an unknown humoral factor or factors.

Quantitative computed tomography: comparative study using different scanners with two calibration phantoms

To assess computed tomography (CT) scanners in vertebral quantitative computed tomography (QCT) measurement, five cadaveric vertebrae fixed in a water phantom were measured using 16 CT scanners of 10 different models using two types (CaCO3 and K2HPO4) of reference phantom. Although the same reference phantoms were used, the QCT values varied markedly depending on the CT scanner employed. The differences in QCT values were greater in the equivalent amount of CaCO3 than in that of K2HPO4. The largest difference between CT scanners was 40 mg/cm3 in the equivalent amount of CaCO3 and 28 mg/cm3 in that of K2HPO4. These differences were reflected among CT scanners by different slopes and intercepts of the reference lines of CaCO3, K2HPO4 and ash density depending on the CT scanner used. However, good correlations (r greater than 0.97) were observed for the QCT values obtained by various CT scanners. These results show that QCT values on one machine can be compared more closely with those of another machine if conversion formulae, determined by using materials equivalent to human vertebral bone, are employed.

Scintigraphy in nontraumatic femoral head necrosis

We performed serial 99mTc-MDP bone scintigraphy of nontraumatic femoral head necrosis in 14 hips of 10 patients. The uptake of isotope was decreased in the very early stage, and either variable or increased at the stage when symptoms appeared. A variable uptake changed to increased uptake in 3 of 10 patients, but there was no hip in which an increased uptake changed to a variable uptake. No relationship was demonstrated between the scintigraphic appearance of the femoral head and the pain and function of the hip.

Reactive endosteal bone formation

The microstructure of reactive endosteal new bone was examined using undecalcified ground sections in five pathologic conditions (bone metastasis from prostate cancer in seven cases, intervertebral osteochondrosis in five, Paget disease in four, chronic suppurative osteomyelitis in two, and fracture healing in one). To determine a basic form of rapid intramembranous bone formation, fetal rat calvaria and primitive bones made in clonal osteogenic cell culture were also observed. In slow bone-forming conditions, lamellar new bone was deposited on pre-existing trabecular surface and caused trabecular thickening on radiographs. In contrast, in rapid bone-forming conditions, woven bone was deposited as spicules extending from trabecular surface so as to form new networks in intertrabecular space. This causes obscurity of trabecular margins radiographically. Reactive endosteal bone formation may be nonspecific and have a significance for assessing the virulence of underlying pathologic conditions like periosteal reactions.

Clinical Features of Aluminum-Associated Bone Disease in Long-Term Hemodialysis Patients

We encountered 11 patients with aluminum-associated bone disease (AABD), and treated them with deferoxamine (DFO). In 3 patients, a second bone biopsy was done during DFO treatment. Clinical features of AABD were compared with surgically proven secondary hyperparathyroidism (2 degrees HPT) with osteitis fibrosa on X-ray. Patients with AABD had disabling bone pain. This disease showed radiological signs ranging from normal, localized bone atrophy, to multiple fractures. It was characterized by increased soft tissue activity and localized abnormal uptake of 99mTc-MDP, detected by skeletal scintigrams. Patients with AABD had low levels of parathyroid hormone and alkaline phosphatase, but high aluminum (Al) levels compared to those with 2 degrees HPT. Serum Al increased after DFO administration, and the patients improved both clinically and histologically. 1-alpha-Hydroxyvitamin D3 (1-alpha-OH D3) was not effective for AABD. We concluded that the administration of antacids containing Al should be minimized in dialysis patients.

Evidence that factors other than 1,25 dihydroxyvitamin D may play a role in augmenting intestinal calcium absorption in patients with primary hyperparathyroidism

SummaryWe examined 17 patients with primary hyperparathyroidism for their serum 1,25 dihydroxyvitamin D levels and for their fractional intestinal calcium absorption rates using a whole body counter and calcium-47. As controls, 10 normal volunteers were examined both before and after administration of 1α-hydroxyvitamin D to increase serum 1,25 dihydroxyvitamin D. Values of serum 1,25 dihydroxyvitamin D were 71.6±37.6 pg/ml (mean ±SD) in patients with primary hyperparathyroidism and 75.3±27.7 pg/ml (mean ±SD) in normal volunteers after administration of 1α-hydroxyvitamin D, while values of intestinal calcium absorption rate were 61.5±16.5% (mean ±SD) in patients with primary hyperparathyroidism and 34.1±5.1% (mean ±SD) in normal controls, respectively. There was a positive correlation between values of serum 1,25 dihydroxyvitamin D and intestinal calcium absorption in both groups. However, in patients with primary hyperparathyroidism, intestinal calcium absorption was more increased than that in normal volunteers when compared to their serum values of 1,25 dihydroxyvitamin D. This suggests that another factor than 1,25 dihydroxyvitamin D plays an important role in the intestinal calcium absorption in patients with primary hyperparathyroidism.

Accumulation of 99mTc-pyrophosphate in a muscle hernia of the thigh

A patient with a muscle hernia in the thigh showed increased muscle uptake of radioactivity during bone imaging using 99mTc-pyrophosphate. The area of excessive accumulation corresponded well to the location and extent of the herniated muscle tissue observed at surgery. Microscopic examination revealed chronic muscle damage, which was assumed to be responsible for the abnormal muscle labelling found in this patient.

Bone mineral measurement by CT apparatus with simultaneous use of reference phantom: Error factors and clinical evaluation

For the purpose of non-invasive quantification of trabecular mineral content of the third lumbar vertebra, quantitative computed tomography (QCT) using reference phantom was conducted. In order to minimize the error, the lumbar spine to be measured should be brought to the center of CT gantry, the phantom should be brought into close contact with the object for measurement, scanning should be carried out on 10mm slice thickness and the ROI (region of interest) should be taken as large as possible, according to our experience. Comparison of QCT values among various CT apparatus was difficult. This method was applied to the measurement of trabecular mineral content of the third lumbar vertebra. In 151 control subjects, the trabecular mineral content of the third lumbar vertebra decreased from the 3rd decade. In the initial adult period, females showed higher trabecular mineral content than males. A rapid loss of trabecular mineral content occurred between the 5th and 6th decade in females, so that after the 7th decade, males had higher trabecular mineral content than females. 47 patients with spinal osteoporosis and 16 patients with fracture of the femoral neck gave significantly lower trabecular mineral content than subjects in the same decade group without those conditions.

Case report 429

Address reprint requests to: Jun Aoki, M.D., Department of Radiology and Nuclear Medicine, Kyoto University School of Medicine, Shogin, Sakyo-ku, Kyoto 606, Japan time of admission demonstrated enlargement of several cervical and inguinal lymph nodes, a small nodule in the skin on the left thoracic wall, and mild hepatomegaly. Laboratory data showed severe hypercalcemia (14.3 mm/dl), hypercalciuria, and elevated levels of serum alkaline phosphatase and lactate dehydrogenase. Renal function was disturbed mildly. Serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D were supressed, and the serum prostaglandin E level in