Efficacy of combined treatment with alendronate (ALN) and eldecalcitol, a new active vitamin D analog, compared to that of concomitant ALN, vitamin D plus calcium treatment in Japanese patients with primary osteoporosis.

UNLABELLED: Combined treatment with alendronate and eldecalcitol was found to be more effective in reducing the bone turnover markers and increasing bone mineral density than alendronate treatment with vitamin D3 and calcium supplementation in the osteoporotic patients. INTRODUCTION: We compared the clinical efficacy and safety of combined treatment with alendronate plus eldecalcitol (ALN + ELD) with those of treatment with ALN plus vitamin D and calcium (ALN + VitD). METHODS: Osteoporotic 219 patients were randomly assigned to the ALN + ELD, or the ALN + VitD group. Primary endpoint was the inter-group differences in lumbar spine BMD (L-BMD) at patient's last visit. Secondary endpoints included the differences in BMD at other sites and the bone turnover marker (BTM) levels. RESULTS: L-BMD, total hip BMD and femoral neck (FN-BMD) increased from baseline by 7.30, 2.41, and 2.70 % in the ALN + ELD group, and by 6.52, 2.27, and 1.18% in the ALN + VitD group, respectively. Inter-group differences of the L-BMD and total hip BMD values were not significant. The increase of the FN-BMD was larger in the ALN + ELD group than the ALN + VitD group. Reductions of the BTMs were greater in the ALN + ELD group than the ALN + VitD group. Interaction of the percent increase of the L-BMD with the baseline values of the BTMs was observed in the ALN + VitD group only. The increases of the FN-BMD in patients with lower baseline values of type-I-collagen C-telopeptide (sCTX) and serum 25(OH) D levels <20 ng/mL were significantly larger in the ALN + ELD group than the other group. CONCLUSION: Combination treatment of ALN plus ELD was more effective in reducing the BTMs and increasing the FN-BMD than ALN treatment with vitamin D3 and calcium.

Effect of the cathepsin K inhibitor odanacatib administered once weekly on bone mineral density in Japanese patients with osteoporosis--a double-blind, randomized, dose-finding study.

UNLABELLED: The efficacy and safety of oral placebo or odanacatib 10, 25, or 50 mg once weekly for 52 weeks were evaluated in a double-blind, randomized, multi-center study in Japanese female and male patients with osteoporosis. INTRODUCTION: Odanacatib is a selective and reversible cathepsin K inhibitor that decreases bone resorption and increases bone mineral density (BMD). METHODS: The primary efficacy endpoint was percent change from baseline to week 52 in lumbar spine BMD. Secondary endpoints included percent change in total hip, femoral neck, and trochanter BMD and in bone biomarkers after treatment for 52 weeks. RESULTS: In this study, 286 patients [94% female, mean age (SD) 68.2 (7.1) years] were included in the analysis. The least-squares mean percent changes from baseline to week 52 in the groups receiving placebo, 10, 25 and 50 mg of odanacatib for lumbar spine (L1~L4) BMD were 0.5, 4.1, 5.7, and 5.9% and for total hip BMD were -0.4, 1.3, 1.8, and 2.7%, respectively. The changes in femoral neck and trochanter BMD were similar to those at the total hip. Bone turnover markers were reduced in a dose-dependent manner. However, the effects of odanacatib on bone formation markers were less compared with the effects on bone resorption markers. Tolerability and safety profiles were similar among all treatment groups with no dose-related trends in any adverse events. CONCLUSIONS: Weekly odanacatib treatment for 52 weeks increased BMD at the lumbar spine and at all hip sites in a dose-dependent manner and was well tolerated in Japanese patients with osteoporosis.

Calcaneus as a site for the assessment of bone mass.

The calcaneus is a skeletal site frequently used for monitoring bone loss after spaceflight, because it is sensitive to microgravity-induced bone mineral loss and reflects the degree of demineralization in the vertebra and the femoral neck. In this article, methods for assessing the calcaneus are reviewed, and their potential applications and limitations as the monitoring site for bone loss in weightlessness are discussed. Currently, single or dual energy X-ray absorptiometry appears to be most sensitive for monitoring bone mineral loss in weightlessness. The results of recent studies suggest two- to threefold longer follow-up times required for ultrasound techniques. However, ultrasound devices can be designed to be portable, making them attractive for inflight use, and ultrasound techniques are expected to provide information related to bone quality. Additional investigations that assess new ultrasound techniques would be important to determine and utilize the full potential of this technology for monitoring bone loss in weightlessness.

Visualization of ocular melanoma with N-isopropyl-p-[123I]-iodoamphetamine.

In a patient with ocular melanoma, scintigraphy with N-isopropyl-p-[123I]-iodoamphetamine [( 123I]IMP) clearly delineated the histologically proven ocular lesion. In a tissue distribution study, using the resected specimen, a significantly high accumulation of the radioactivity was confirmed in tumor tissue. Thus, [123I]IMP scintigraphy provided specific localization of an ocular melanoma.

Metastatic medullary thyroid cancer: localization with iodine-131 metaiodobenzylguanidine.

A patient in whom metastatic medullary thyroid cancer was diagnosed underwent a scintigraphic examination using [131I]MIBG. Multiple hot lesions and diffuse hepatic uptake were noted corresponding to bone and liver metastases. Iodine-131 MIBG may prove to be useful for scintigraphic localization and for the treatment of medullary thyroid cancer as in pheochromocytoma and neuroblastoma.

Bone mineral measurement in Japan.

Various methods for evaluating bone mineral in appendicular, and axial bone or in the whole skeleton have recently become available. As bone mineral is one of the major determinants of bone strength, its exact measurement should be useful for the diagnosis of osteoporosis, as well as for the prediction of fracture risk and monitoring of therapeutical response. The aims of this paper are to review the fundamental performance of bone mineral measurements, the improvements in DXA systems, and the progress in site-specific bone mineral instruments for the radius and calcaneus used in Japan, and to introduce diagnostic criteria for primary osteoporosis, and report on annual rates of bone loss in Japanese females.

Accumulation of 99mTc-HM-PAO in photon deficient areas in bone scan of bone metastasis from hepatocellular carcinoma.

To evaluate bone metastasis from hepatocellular carcinoma (HCC), both bone and 99mTc-HM-PAO scintigraphies were performed in six patients with clinically and pathologically confirmed HCC. Two patients had a bone scintigram which revealed abnormal accumulation in the skull base, pelvic bone and thoracic spine. The 99mTc-HM-PAO scans of both these patients also showed abnormal accumulation in the same sites. The bone scintigrams in one patient revealed not only abnormal accumulation in the ribs but also photon deficient areas in the sternum, thoracic spine and femur, while 99mTc-HM-PAO scans showed abnormal accumulation in all these sites. In three patients, bone scintigraphy revealed photon deficient areas in the ribs, pelvic bone and femur, and their 99mTc-HM-PAO scintigrams showed abnormal accumulation in the same sites. Thus, it was shown that, in the detection of bone metastasis from HCC by means of bone scintigraphy, it was necessary to pay attention to hot and cold lesions, and that a combination study with 99mTc-phosphorous compounds and 99mTc-HM-PAO was useful in evaluating these lesions.

A fundamental study of a computed X-ray densitometry system for bone mineral measurement in the second metacarpal bone.

The effect of radiographic exposure factors such as the photographic film density, X-ray tube voltage, and focus-film distance on the indices of bone mineral obtained by computed X-ray densitometry (CXD), a newly developed X-ray microdensitometric system, was investigated. sigma GS/D, which corresponded to the bone mineral density divided the integrated bone mineral by the bone width of the second metacarpal bone, was influenced by these exposure factors, whereas MCI, which represented the ratio of the cortical bone to whole bone, was independent of them. Present results indicated that the focus-film distance between 85 and 115 cm, the X-ray tube voltage in 45-60 kV, and a photographic density of lower than 1.82-1.86 of the screen-film combination should be used to assess quantitatively bone mineral of the second metacarpal bone using the CXD system.

Indexes of bone mineral content on second metacarpal bone roentgenogram analyzed by digital image processing: a comparison with other bone mass quantifying methods.

A new photodensitometric technique (digital image processing, DIP) was performed to assess the bone mineral content of the metacarpal bone as a screening test for bone loss in 340 healthy or osteoporotic women as well as 35 steroid-dosed patients and 46 patients with chronic renal failure on hemodialysis. This procedure was compared with single photon absorptiometry and dual photon absorptiometry in terms of clinical value. Two bone mineral indexes, metacarpal index and sigma GS/D (the integrated bone mineral density of cortical and trabecular bone on a cross section in the middle of the second metacarpal bone), were equal to other methods in the quantification of decreases in bone mineral content due to aging in healthy or osteoporotic women. In addition, sigma GS/D was sensitive enough to detect decreases in bone mineral content in patients with vertebral fractures, on steroid therapy, and with chronic renal failure. Thus, sigma GS/D measured by DIP was shown to have clinical value as a tool in screening for decreased bone mineral content.

Determination of vertebral bone mineral density with new dual energy X-ray absorptiometry using multiple detectors: fundamental studies.

Fundamental studies on the ability of a newly developed 90-detector dual energy X-ray absorptiometry (DEXA) system with a fan beam, the DCS-3000, to determine bone mineral density (BMD) were performed. This new system not only measured BMD precisely, resulting in a fast scan mode in CV of 0.89% and 1.63% for in vitro and in vivo studies, respectively, but also performed data acquisition in a greatly reduced examination time (24 sec). Furthermore, when a rod phantom was used, the linear regression equation obtained between BMD quantified with the QDR-1000 (x) and that quantified with the DCS-3000 (y) was y = 1.250x-0.242. In both healthy subjects and osteoporotic patients, significant positive correlations were obtained between radial BMD and vertebral BMD measured with the QDR-1000 and with the DCS-3000. The correlation for radial BMD was r = 0.533 (p less than 0.001, N = 76), and that for vertebral BMD was r = 0.985 (p less than 0.001, N = 56). Therefore, in addition to safety of operation, the performance of the DCS-3000 was considered to be equal to that of commercially available DEXA systems, indicating that it should be useful in the detection of vertebral bone loss.

Confirmation of dialysate leakage by intraperitoneal administration of radioactive colloid.

A 29-year-old man who had been on continuous ambulatory peritoneal dialysis (CAPD) was admitted to our hospital because of pleural effusion. Radioactive colloid studies with intraperitoneal administration revealed a pleuroperitoneal communication. After pleurodesis by the administration of fibrin glue and antiplasmin into the thoracic cavity, the pleural effusion did not reaccumulate and there was no evidence of pleuroperitoneal communication by radioactive colloid study.

Usefulness of liver scan using 99mTc-phytate in diagnosis of partial diaphragmatic eventration.

Partial diaphragmatic eventration, when occurring at uncommon sites, is difficult to diagnose when only using a plain X-p and fluoroscopy. We experienced an unusual variety of this disorder. In order to diagnose this case, liver scintigraphy using 99mTc-phytate was performed, and we were able to make a definite diagnosis without other invasive examinations.

A case of synovial sarcoma with bone metastasis identified by bone marrow scintigraphy.

In a patient with synovial sarcoma, routine bone survey showed no abnormality, while bone marrow scintigraphy with Tc-99m sulfur colloid revealed a defect in the fifth lumbar vertebra. At surgery, tumorous invasion was noted in the fifth lumbar vertebra and the surrounding tissues. It was suggested that the bone marrow scintigraphy was particularly useful in the detection of tumorous invasion into the bone marrow at the early stage before the destruction of skeletal tissue.

Visualization of soft tissue by technetium-99m MDP in polymyositis. Case reports.

Two patients with polymyositis showed abnormal muscular uptake of Tc-99m-methylene diphosphonate (MDP) during routine bone imaging. Imaging with Tc-99m MDP is a useful tool in monitoring the activity of the diseased muscle.

Usefulness of bone imaging in diagnosis of sternocostoclavicular hyperostosis.

Four patients with sternocostoclavicular hyperostosis showing characteristic abnormal uptake on bone imaging are described. Bone imaging was useful in the diagnosis of sternocostoclavicular hyperostosis.

New perspectives for diagnosis of nodular goiter by technetium-thallium subtraction scanning.

To improve the scintigraphic differential diagnosis of thyroid nodules, Tc-99m pertechnetate-Tl-201 Cl subtraction scintigraphy (Tc-Tl subtraction scanning) was performed in 106 patients with various histologically proven thyroid nodules. Results were evaluated by comparison with surgical findings and preoperative ultrasonographic results. Thyroid nodules were more successfully detected by Tc-Tl subtraction scanning than by either Tc-99m pertechnetate or Tl-201 Cl scintigraphy alone. Detection of nodules was further improved when images recorded by the three methods were integrally observed (sensitivity 83%, accuracy 89%), with detectability approaching that of ultrasonography. False-positive or -negative Tc-Tl subtraction scans were obtained principally when multiple nodules were present (7 cases) or when no discrepancy existed between the accumulations of Tc-99m pertechnetate and Tl-201 Cl (18 cases). Most colloid nodules exhibited irregular margins, heterogeneous internal accumulations of Tl-201 Cl, and distorted shapes on Tc-Tl subtraction scans, while the majority of adenoma were oval-shaped with smooth margins. Carcinoma were characterized by homogeneous internal accumulation of Tl-201 Cl and distorted shapes.

[Comparative study on the tumor accumulation of 99mTc-tetrofosmin and 99mTc-MIBI in rabbits bearing VX-2 cancer].

Each of myocardial blood flow imaging agents has a potential usefulness as an agent for tumor scintigraphy. The tumor accumulation and washout of 99mTc-tetrofosmin and 99mTc-MIBI were comparatively studied using rabbits bearing VX-2 cancer. From seventeen to twenty days after the implantation of VX-2 cancer into the femoral region of seven rabbits, tumor to soft tissue accumulation ratio (T/S ratio) of each agent was calculated in early images (5 min after injection) and in late images (50 min after injection). Compared with 99mTc-tetrofosmin, the T/S ratio of 99mTc-MIBI was higher and, moreover, the washout was delayed. These results suggest that there is a difference in tumor accumulation property between these two agents.

[Usefulness of 67Ga scintigraphy in deciding surgical indication in secondary hyperparathyroidism].

In order to evaluate the usefulness in deciding surgical indication in secondary hyperparathyroidism (SHP), 67Ga scintigraphy was performed in 37 patients of SHP before parathyroidectomy (PTx). The radionuclide accumulation in skull and submandible was classified into 4 patterns (skull-submandibular pattern, skull pattern, submandibular pattern and normal pattern). Serum alkaline phosphatase levels were significantly elevated in patients of skull-submandibular pattern (13 cases) compared with skull pattern (6 cases), submandibular pattern (6 cases) and normal pattern (12 cases). Serum intact parathyroid hormone levels were significantly elevated in patients of skull-submandibular and skull patterns compared with normal pattern. No significant difference was observed among the weight of resected parathyroid glands. In 4 of 6 patients of normal pattern on 67Ga scintigram, bone scintigraphy showed a characteristic pattern of SHP including an increased accumulation in the skull and submandible. Bone mineral density (BMD) in the distal radius was increased within six to twelve months after PTx in 10 of 11 patients of skull-submandibular pattern on 67Ga scintigram, whereas only one patient showed an increase in BMD in 9 patients of normal pattern. In summary, it was concluded that 67Ga scintigraphy could provide a useful information in deciding the indication for PTx in secondary hyperparathyroidism.

[Single photon emission computed tomography (SPECT) using 99mTc-hexamethyl propyleneamine oxime in patients with ischemic cerebral diseases: comparative study of N-isopropyl-p-[123I]-iodoamphetamine and 99mTc-DTPA SPECT].

In order to confirm the diagnosis and clarify the pathophysiology in the ischemic lesions in brain, 99mTc-PAO SPECT was performed in 42 patients with ischemic cerebral diseases, and the findings on 99mTc-PAO SPECT were compared with those on 123I-IMP or 99mTc-DTPA SPECT, and on X-CT. Furthermore, count ratio of ischemic lesion to normal contralateral region (I/N) was used for the evaluation of the detectability in the lesions on 99mTc-PAO or 123I-IMP SPECT, and less than 0.95 of I/N ratio was defined as the decreased accumulation. The detectability of ischemic lesion in brain with 99mTc-PAO SPECT was 80%, which was superior to that (60%) of LDA on X-CT. Especially, 99mTc-PAO SPECT was useful in cases which were examined early after the onset of the attack. On the other hand, 123I-IMP SPECT showed the best result (88%) in the detectability, and furthermore I/N ratio on 123I-IMP SPECT was lower than that on 99mTc-PAO SPECT. In the delayed phase on 123I-IMP SPECT the redistribution was observed in 30%, while on 99mTc-PAO SPECT it was done in none of them. The accumulation of 99mTc-DTPA in brain was found in 6 of 14 cases (43%), and 2 cases among them also showed the accumulation of 99mTc-PAO in the ischemic lesion. In such cases the destruction of BBB might be considered as the cause of the accumulation of 99mTc-PAO. Thus, 99mTc-PAO SPECT was thought to be useful method in clinical studies of the ischemic cerebral diseases.