Nutritive value of Geotricum candidum yeast prepared from decaying fruits in Egypt

Quantitative histology of thin, nondecalcified sections was performed on sequential bone biopsy specimens from five patients undergoing long-term hemodialysis and treated with calcifediol (25-hydroxycholecalciferol) for periods of three to nine months. With increase of intestinal absorption of calcium and decline of circulating immunoreactive parathyroid hormone and alkaline phosphatase, the bones of each patient exhibited striking histological improvement. The group as a whole showed statistically significant decreases in osteoclast number and in the percentages of osteoid surface covered by active osteoblasts. Marrow fibrosis was either eliminated or strikingly decreased in each patient. Osteoid volume significantly declined in four of five patients. In patients with osteitis fibrosa as the predominant histological lesion, calcifediol therapy resulted in decreased calcification front activity. Increased activity was the result when osteomalacia predominated.     

Immunoreactive parathyroid hormone, 25-hydroxycalciferol and bone histology in renal osteodystrophy (author's transl)

Immunoreactive parathyroid hormone (iPTH) and 25-hydroxycalciferol (25(OH)D) serum levels were determined in 32 patients with renal osteopathy, they were correlated with the results of bone biopsy and other clinical parameters. iPTH was closely related to bone histology, it did not correspond to serum calcium and alkaline phosphatase, but the correlation to serum phosphate was statistically significant. 25(OH)D levels were not related to the histological findings of osteomalacia or increased bone resorption, while a correlation between the vitamin D metabolite and serum calcium could be observed. Since iPTH and 25(OH)D levels exhibited a significant correlation, an inhibitory effect of 25(OH)D on parathyroid gland function in renal failure was discussed.     

Hypophosphataemic osteomalacia in fibrous dysplasia

We describe three patients with fibrous dysplasia of bone in whom there was evidence of hypophosphataemic osteomalacia or rickets. Two of the patients had polyostotic fibrous dysplasia and osteomalacia. The third was a child with fibrous dysplasia of the facial and cranial bones and rickets. In all cases the manifestations of osteomalacia or rickets were controlled with large doses of vitamin D. In the child the rickets and hypophosphataemia ceased when most of the bone affected by fibrous dysplasia was surgically resected. Previously reported cases of the association between fibrous dysplasia and hypophosphataemic osteomalacia are reviewed. We suggest that these cases are analogous to the syndrome of 'tumour rickets' where hypophosphataemia appears to be due to the presence of a mesenchymal tumour and regresses when the tumour is removed.     

Osteomalacia cured by resection of cutaneous neurinoma

INTRODUCTION: Regression of osteomalacia after exeresis of a skin tumor is unusual. CASE REPORT: A 62-year-old man had suffered from bone and joint symptoms for several years due to osteomalacia which was confirmed both biologically and histologically. The patient also had a plantar neurinoma. After exeresis of the tumor the biological results returned to normal levels within one week followed by regression of the clinical signs of osteomalacia. DISCUSSION: The neurinoma in this patient was apparently the cause of osteomalacia, since signs of the disease disappeared after exeresis. To date, three cases of neurinoma associated with osteomalacia have been published, including a single case with skin localization. The tumor would secrete a substance which inhibits the synthesis of vitamin D and enhances phosphorus excretion.     

Orthopedic aspects of metabolic bone disease

Although metabolic bone disorders are common, they may be difficult to distinguish on the basis of clinical and radiologic findings. Understanding their diverse manifestations on imaging studies may allow early diagnosis. This article discusses osteoporosis, osteomalacia, rickets, hyperparathyroidism, hypothyroidism, hyperthyroidism, renal osteodystrophy, and Paget disease, with emphasis on radiologic differential diagnosis.     

Study on vascular calcification in patients on continuous ambulatory peritoneal dialysis (CAPD): special reference to active vitamin D (VD) treatment

Cardiovascular complications, such as vascular calcification (VC), have been a major concern in patients undergoing chronic dialysis. The pathogenesis of this VC has been attributed to the altered calcium and phosphate metabolism, but the contributing factors have not been clarified. In order to investigate these factors, 38 CAPD patients were divided into two sub-groups according to the absence of aortic calcification (Group-A; n = 18) or the presence of aortic calcification (Group-B; n = 20). The number of elderly patients was larger and the duration of CAPD was longer in Group-B than in Group-A. Calcium and phosphate metabolism and serum lipids levels did not differ significantly between groups and the number of patients given VD was 8/18 in Group-A and 14/20 in Group-B. In order to explore the progression of VC in CAPD patients given long-term treatment with VD, 22 patients who were matched for the duration of CAPD were analyzed. These were divided into two sub-groups according to whether they were treated with VD (Group-C; n = 11) or not treated with VD (Group-D; n = 11). Radiological findings (such as the degree of aortic calcification), bone mineral content, divalent ions, parathyroid hormone levels and lipid profiles were examined. The prevalence of patients with aortic calcification was significantly higher in Group-D than in Group-C (7/11 v. s. 2/11, P < 0.05). However, lipids, mineral and endocrinological parameters did not differ between the sub-groups. No significant difference in the calcium and phosphate balance was observed. The bone mineral content revealed no difference between both of the sub-groups. VD administration by conventional mode, even without significant suppression of PTH or increase of bone mineral content, may enhance vessel calcification in patients on long-term CAPD.     

Biological and histological profile of osteomalacia in condensing prostatic osteosis. Apropos of 4 cases

The authors report on 4 cases of condensating prostatic osteosis, whose biological picture and histomorphometric lesions in the involved area indicate osteomalacia. They discuss the individual nature of such a syndrome, the links between vitamin D deficiency and hyperosteoidosis at a very slow noted speed of calcification, and the usefulness of investigating and treating the syndrome.     

The primary calcification in bones follows removal of decorin and fusion of collagen fibrils

To elucidate the mechanisms of primary calcification in bone, ultrastructural changes in collagen fibrils, as well as cytochemical alteration of proteoglycan, especially decorin, were investigated morphologically in 19-day postcoitum embryonic rat calvariae. Below the osteoblast layer, calcification of the osteoid area increased in direct proportion to its distance from the osteoblasts. In the uncalcified osteoid area, collagen fibrils near matrix vesicles possessed sharp contours and were a uniform 50 nm in diameter. Immunoelectron microscopy revealed decorin to be abundantly localized in the vicinity of the collagen fibrils. In the osteoid area undergoing the process of calcification, collagen fibrils tended to fuse side by side. Where calcification was progressed, this fusion was even more so. Some very large fibrils exhibited complicated contours, 400 nm or more in diameter. Although the calcification at this stage affected areas both inside and outside of the collagen fibrils, the interior areas manifested a lower density of calcification. The immunolocalization of decorin was also much decreased around these fibrils. Thus, primary calcification in bone matrix follows the removal of decorin and fusion of collagen fibrils. This phenomenon may aid in the process of calcification and bone formation, because (1) inhibitors of calcification, such as decorin, are removed, (2) the fusion of collagen fibrils provides the room necessary for rapid growth of mineral crystals, and (3) the soft elastic bone matrix containing abundant fused collagen fibrils less subjective to calcification is safe for both maternal and embryonic bodies and is convenient for subsequent bone remodeling.     

osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification

Osteoprotegerin (OPG) is a secreted protein that inhibits osteoclast formation. In this study the physiological role of OPG is investigated by generating OPG-deficient mice. Adolescent and adult OPG-/- mice exhibit a decrease in total bone density characterized by severe trabecular and cortical bone porosity, marked thinning of the parietal bones of the skull, and a high incidence of fractures. These findings demonstrate that OPG is a critical regulator of postnatal bone mass. Unexpectedly, OPG-deficient mice also exhibit medial calcification of the aorta and renal arteries, suggesting that regulation of OPG, its signaling pathway, or its ligand(s) may play a role in the long observed association between osteoporosis and vascular calcification.     

Heterotopic implantation of mouse bone-marrow cells: an in vivo model allowing analysis of mineral phases during mineralization processes

Heterotopic calcification induced after implantation of bone-marrow cells under the murine kidney capsule was used to study the mineral phases occurring during the mineralization process. Ossicles were found to contain numerous osteoblastic cells that produced an organic matrix closely associated with active hematopoietic tissue. During implantation of bone marrow, needle-shaped microcrystals were progressively deposited on collagen fibers. The mineral formed in the heterotopic calcification consisted mainly of calcium phosphate. The distribution and density of the microcrystals were heterogeneous after 6 weeks of implantation but became homogeneous and well-crystallized after 10 weeks. The Fourier transform infrared microspectroscopy provided important spatial data on the nature of the mineral formed and the changes in the mineral environment. Similarities were noted between young bone (bone callus) and 6-week heterotopic ossicles, and between adult bone and 10- or 12-week heterotopic ossicles. The study demonstrated that murine heterotopic calcification under the renal capsule can be a very useful model for studying bone apatite formation during the mineralization process.     

Metastatic calcification: the role of bone scanning

Metastatic calcification involving the lungs and stomach was demonstrated in 3 patients by bone scans. In one patient, postmortem studied five days later confirmed the findings. Follow-up scans in 2 patients, demonstrating improvement in one and worsening in another, paralleled the clinical course.     

A detailed protocol for the measurement of TGF-beta1 in human blood samples

Bisphosphonates are compounds derived from pyrophosphate, a byproduct of cellular cleavage of adenosine triphosphate (ATP), and are resistant to alkaline phosphatase by virtue of replacement of oxygen by carbon. The high affinity of the P-C-P structure for hydroxyapatite accounts for deposition in bone. Modification of the two side chains of carbon alters the potency of the drugs. Of those that have either completed or are undergoing clinical trials, the order of increasing potency for inhibition of bone resorption is etidronate, clodronate, tiludronate, pamidronate, alendronate, residronate and ibandronate (potency range: 1 to 10,000). Less than 5% of bisphosphonates are absorbed and the half life is a few hours. The drugs must be given on an empty stomach because food and beverages interfere with gastrointestinal absorption. Of the absorbed fraction, as much as 60% is taken up by the skeleton and the remainder is excreted unchanged in the urine. Etidronate, tiludronate, residronate, and alendronate are given orally, clodronate intravenously, and pamidronate and ibandronate by either route. At lower concentrations, bisphosphonates inhibit osteoclatic bone resorption, whereas at higher concentrations they may inhibit mineralization and cause osteomalacia. Inhibition of mineralization diminishes with increasing potency. In postmenopausal women, etidronate and alendronate for 3 yr were shown to inhibit bone resorption, increase bone mineral density (BMD) of the lumbar spine and hip, and prevent fractures without producing osteomalacia. Bone formation also is reduced as a consequence of diminished bone resorption but reduction is less than the reduction of bone resorption. In higher doses bisphosphonates may cause upper gastrointestinal disturbances but in recommended doses they generally are well tolerated and have an excellent safety profile.     

Systematic assessment of bone resorption, collagen synthesis, and calcification in chick embryonic calvaria in vitro: effects of prostaglandin E2

A systematic method has been developed to assess bone resorption, matrix formation, and calcification in a single calvarial culture from 20-day-old chick embryos. The bones were prelabeled with 45Ca by an injection into the egg white before culture. In the last 2 h of incubation, the bones were further labeled with both 3H-proline and 3H-tetracycline. Bone resorption was assessed as 45Ca release into the medium. Collagen synthesis was measured by the incorporation of 3H-proline into collagenase-digestible protein (CDP). Since tetracycline has been commonly used as an in vivo marker for osteoid calcification, we assessed in vitro calcification as the uptake of 3H-tetracycline into bone. By using this method, we studied the effects of prostaglandin E2 (PGE2) and indomethacin, which inhibits biosynthesis of PGE2, on bone resorption and formation. The cultured bone synthesized approximately 300 ng of PGE2 during every 24 h of incubation, and indomethacin (10(-6) M) completely inhibited the synthesis. In indomethacin-treated cultures, % 45Ca release and the labeling of CDP were significantly reduced. These reductions were not seen when exogenous PGE2 (10(-9) M) comparable to its endogenous level was added along with the indomethacin. Furthermore, 10(-8) to 10(-5) M PGE2 increased % 45Ca release and the CDP labeling. In addition, the uptake of 3H-tetracycline into the cultured bone was also enhanced by PGE2. In devitalized calvaria, PGE2 had no effect on 3H-tetracycline uptake, suggesting that the stimulative effect on PGE2 was cell-mediated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Calcium metabolism, osteoporosis and essential fatty acids: a review

Essential fatty acid (EFA)-deficient animals develop severe osteoporosis coupled with increased renal and arterial calcification. This picture is similar to that seen in osteoporosis in the elderly, where the loss of bone calcium is associated with ectopic calcification of other tissues, particularly the arteries and the kidneys. Recent mortality studies indicate that the ectopic calcification may be considerably more dangerous than the osteoporosis itself, since the great majority of excess deaths in women with osteoporosis are vascular and unrelated to fractures or other bone abnormalities. EFAs have now been shown to increase calcium absorption from the gut, in part by enhancing the effects of vitamin D, to reduce urinary excretion of calcium, to increase calcium deposition in bone and improve bone strength and to enhance the synthesis of bone collagen. These desirable actions are associated with reduced ectopic calcification. The interaction between EFA and calcium metabolism deserves further investigation since it may offer novel approaches to osteoporosis and also to the ectopic calcification associated with osteoporosis which seems to be responsible for so many deaths.     

Tuberculosis of the chest wall: CT findings

To assess the CT features of tuberculosis of the chest wall, the CT findings in four patients with documented tuberculous chest wall infection were reviewed. Two patients were Caucasian and two were of Chinese origin. All had normal immune status. In two cases tuberculosis involved the ribs, in one the costal cartilage, and in one the sternoclavicular joint. Computed tomography demonstrated osseous and cartilaginous destruction (in four), soft tissue masses with calcification (in two), and rim enhancement following intravenous contrast medium administration (in two). Underlying pleuroparenchymal tuberculosis was present in two cases. Tuberculosis of the chest wall is characterized by bone or costal cartilage destruction and soft tissue masses that may demonstrate calcification or rim enhancement with or without evidence of underlying lung or pleural disease.     

Metastatic pulmonary, gastric, and renal calcification demonstrated on bone scintigraphy in a patient with malignant melanoma and renal failure

PURPOSE: This case report describes the clinical, scintigraphic, and pathologic findings in a patient with an unexpected finding of a cutaneous malignant melanoma. METHOD: Multiple imaging studies were done, as was a pathologic examination of a suspicious pigmented lesion on the patient's back. RESULT: A Tc-99m MDP bone scan showed diffuse uptake in the skeleton, lungs, kidneys, and stomach. CONCLUSION: Metastatic calcification, as shown by isotope scintigraphy, is an unusual manifestation of metastatic cancer from a primary cutaneous melanoma.     

Effect of dietary selenium and vitamin E on the biomechanical properties of rabbit bones

It is generally agreed that combined deficiency of selenium and vitamin E leads to several abnormalities including Kashin-Beck disease which is an endemic and chronic degenerative osteoarthrosis. The abnormalities can be reversed by the administration of various forms of selenium and vitamin E. The present study was designed to investigate the effects of dietary selenium and vitamin E on bone tissue and on the biomechanical properties of bone. Young rabbits of both sexes were fed with either a selenium- and vitamin E-adequate diet (control group), or a selenium- and vitamin E-deficient diet or a selenium-excess diet. The selenium-deficient diet resulted in a significant decrease in plasma selenium level and the selenium-excess diet resulted in a significant increase in the plasma selenium level with respect to the corresponding control values (p < 0.05). The diets did not affect the blood cell counts considerably but erythrocyte glutathione peroxidase activity increased (decreased) relatively when the plasma selenium level increased (decreased) (p < 0.05). The light microscopic investigations of the bone tissues of the two experimental groups indicate that the findings of the present work are compatible with osteomalacia. The biomechanical properties of the bones from the three groups were determined experimentally with bending tests. Both the Se- and vitamin E-deficient diet and the Se-excess diet decreased the biomechanical strength of the bones significantly while the bones belonging to the control group always had the largest modulus of elasticity (p < 0.05).     

Stapes fixation associated with symphalangia

We describe a 10-year-old boy and his 9-year-old sister, both of whom had bilateral hearing loss associated with ankylosis of the proximal interphalangeal joints (symphalangia). They had no other abnormal findings except hearing loss and ankylosis of the joints of some fingers and toes on systemic examination. The cause of conductive hearing loss in both cases was bony fusion between the stapes and the bone of the oval window niche. There were no other anatomical abnormalities in the middle or the external ear. The patients' hearing improved markedly after stapes surgery. Histopathologic examination of the stapes revealed an abnormal zone of ossification near the anterior annular ligament and calcification in the annular ligament, which seemed to be the cause of the stapes fixation.     

Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein

Calcification of the extracellular matrix (ECM) can be physiological or pathological. Physiological calcification occurs in bone when the soft ECM is converted into a rigid material capable of sustaining mechanical force; pathological calcification can occur in arteries and cartilage and other soft tissues. No molecular determinant regulating ECM calcification has yet been identified. A candidate molecule is matrix GLA protein (Mgp), a mineral-binding ECM protein synthesized by vascular smooth-muscle cells and chondrocytes, two cell types that produce an uncalcified ECM. Mice that lack Mgp develop to term but die within two months as a result of arterial calcification which leads to blood-vessel rupture. Chondrocytes that elaborate a typical cartilage matrix can be seen in the affected arteries. Mgp-deficient mice additionally exhibit inappropriate calcification of various cartilages, including the growth plate, which eventually leads to short stature, osteopenia and fractures. These results indicate that ECM calcification must be actively inhibited in soft tissues. To our knowledge, Mgp is the first inhibitor of calcification of arteries and cartilage to be characterized in vivo.