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PubMed1992

Bone mastocytosis. A report of nine cases with a bone histomorphometric study.

Bone mastocytosis is characterized radiographically in some patients by diffuse osteosclerosis and in others by demineralization. The reason for these apparently conflicting bone features is unknown. Bone remodeling and marrow mastocytosis infiltration were studied in nine cases of mastocytosis with bone marrow involvement. Six men, ranging from 42 to 78 years of age, and three women, 43, 55, and 73 years old, comprised the series. Two patients had severe and diffuse osteosclerosis. Seven had diffuse demineralization, with crushed vertebrae in four, suggesting common osteoporosis. In three of the seven, cutaneous mastocytosis was absent. Bone biopsies were undecalcified and stained with toluidine blue. In the seven patients with demineralization, the number of marrow mastocytes was increased (154 +/- 24 versus 2 +/- 0.5/mm2 in normal postmenopausal osteoporosis). Mastocyte nodules covering 1-9% of the marrow area were present in all seven patients. These patients showed a significant increase in remodeling; bone formation rate was increased, coupled with a decrease in mean wall thickness. Concomitantly, osteoclast surfaces were increased, with an increased amount of bone resorbed. The two patients with diffuse osteosclerosis had a markedly different histology; mast cell infiltration was dramatically increased (mastocyte count greater than 1000/mm2) with diffuse marrow fibrosis. Bone volume was increased as well, and most of the bone was woven with an intratrabecular mineralization defect. High bone remodeling and decreased osteoblast activity can explain bone loss in mastocytosis with demineralization. Mastocytosis with osteosclerosis is characterized by a more extensive marrow mast-cell infiltration and fibrosis.

Adult↗
PubMed1993

Radiological spectrum of endemic fluorosis: relationship with calcium intake.

Skeletal fluorosis continues to be endemic in many parts of India. Osteosclerosis and interosseous membrane calcification have long been regarded as hallmarks of this disease. Our study showed in addition a wide variety of radiological patterns: coarse trabecular pattern, axial osteosclerosis with distal osteopenia and diffuse osteopenia. Subjects with osteopenic changes had a significantly lower dietary intake of calcium than those groups having normal radiological findings, predominant osteosclerosis or coarse trabecular pattern (p < 0.001, p < 0.01, and p < 0.01 respectively). This suggests the role of calcium intake in determining the skeletal changes in endemic fluorosis.

Adolescent↗
PubMed1977

Partial body calcium measurements on patients with renal failure.

The bone calcium status of 39 patients with chronic renal failure on hemodialysis has been measured by in vivo neutron activation analysis (IVNAA) and reported in terms of a calcium bone index (CaBl) which relates the calcium in a patient to that in a normal person of the same height. In 20 of the 39 cases sequential measurements were made over periods of up to 40 mo. The results are compared with data obtained by radiology and by histological examination of bone biopsies. CaBl values varied from below normal to, in one case, above the range of normal. Many of the higher values were associated with demonstrable osteosclerosis. As found in previous work here with IVNAA, significantly low values of CaBl were associated with vertebral deformities; however, some patients with deformity had normal CaBl values, indicating that these had both local mineral loss (resulting in fracture) and osteosclerosis. Taken all together, the data suggest that more than half the patients have osteosclerosis. Sequential data showed no uniform response to treatment.

Adult↗
PubMed1996

Decreased cortical and increased cancellous bone in two children with primary hyperparathyroidism.

The basis for this study is two children with primary hyperparathyroidism (PHPT) who radiographically manifested both marked subperiosteal resorption and prominent osteosclerosis. We hypothesize that the parathyroid hormone (PTH) elevation not only increased osteoclastic resorption of cortical bone but also simultaneously enhanced cancellous bone formation, giving rise to osteosclerosis. In this report, we describe the changes in trabecular and cortical bone density, as measured by quantitative computed tomography (QCT), in these two young patients with severe PHPT, before and after removal of a parathyroid adenoma. Before surgery, the radiographic findings of subperiosteal resorption and osteosclerosis were associated with low cortical and high cancellous bone density values in both children. Within 1 week of surgery, both cortical and cancellous bone density values increased and serum concentrations of calcium and, to a lesser degree, phosphorus decreased due to the "hungry bone syndrome." Twelve weeks after parathyroidectomy, QCT bone density values and skeletal radiographs were normal in both patients. The findings suggest that in patients with severe PHPT, the catabolic effect of PTH on cortical bone may be associated with a simultaneous anabolic effect on cancellous bone, and PTH may cause a significant redistribution of bone mineral from cortical to cancellous bone.

Adenoma↗
PubMed1973

Azotaemic renal osteodystrophy: a quantitative study on iliac bone.

The histopathology of bone is described in 60 patients with chronic renal failure due to a variety of renal diseases. Changes of azotaemic renal osteodystrophy included osteitis fibrosa, osteomalacia, and osteosclerosis. Quantitative histology using a point-counting technique revealed a significant increase in total bone, mineralized bone, and osteoid in comparison with a control group of 68 individuals. Osteitis fibrosa due to secondary hyperparathyroidism occurred in 93%, osteomalacia in 40%, and osteosclerosis in 30% of patients. Woven bone formation was a characteristic feature and was related to the severity of osteitis fibrosa. There were significant correlations between the weights of parathyroid glands and the number of osteoclasts, amounts of woven bone, and marrow fibrosis in the ilium. Hyperparathyroidism caused degradation of mineralized bone but the loss was balanced or exceeded by the aggradation of woven mineralized bone. Woven bone formation together with excess osteoid gave rise to osteosclerosis. The histological findings indicate that hyperparathyroidism and osteitis fibrosa usually occur early in chronic renal failure and that osteomalacia develops subsequently.

Adult↗
PubMed2005

An autosomal dominant high bone mass phenotype in association with craniosynostosis in an extended family is caused by an LRP5 missense mutation.

Gain-of-function mutations in LRP5 have been shown to cause high BMD disorders showing variable expression of some clinical symptoms, including torus palatinus and neurological complications. In an extended family, we were able to add craniosynostosis and developmental delay to the clinical spectrum associated with LRP5 mutations. We report on an extended four-generation family with 13 affected individuals (7 men and 6 women) in which an autosomal dominant type of osteosclerosis segregates. Osteosclerosis was most pronounced in the cranial base and calvarium, starting in early childhood with variable expression and a progressive character. Craniosynostosis at an early age was reported in four affected family members (two males and two females). The patients also presented with dysmorphic features (macrocephaly, brachycephaly, wide and high forehead, hypertelorism, prominent cheekbones, prominent jaw). They have normal height and proportions. Neurological complications like entrapment of cranial nerves resulting in optical nerve atrophy, hearing loss, and facial palsy were reported in two individuals. A mild developmental delay was reported in three affected individuals. None of the patients have torus palatinus, increased rate of fractures, osteomyelitis, hepatosplenomegaly, or pancytopenia. A missense mutation 640G-->A (A214T) in the low-density lipoprotein receptor-related protein 5 (LRP5) gene was found in all affected individuals analyzed, including cases in whom craniosynostosis, a mild developmental delay, and/or macrocephaly is observed. To our knowledge, this is the first report in the literature of patients presenting with autosomal dominant osteosclerosis in whom a variable expression of craniosynostosis, macrocephaly, and mild developmental delay is observed, which is most likely associated with a mutation in the LRP5 gene. These phenotypes can therefore be added to the clinical spectrum of LRP5-associated bone disorders.

Adult↗
PubMed1994

Endemic fluorosis of the skeleton: radiographic features in 127 patients.

OBJECTIVE: A wide range of radiographic appearances have been reported in skeletal fluorosis, but little has been written about the spectrum of radiographic features. We evaluated the spectrum of radiographic appearances in this disorder to help with its diagnosis and differentiation from other metabolic skeletal disorders. MATERIALS AND METHODS: One hundred twenty-seven patients with clinically proved endemic fluorosis had radiographs of the chest, spine, pelvis, elbow, forearm, and knee obtained. The radiographic findings were classified as osteosclerosis, osteopenia, intermittent growth lines, diaphyseal widening, or soft-tissue ossification. Two different osteopenic patterns were defined: an osteoporotic pattern with overall decreased bone density and an osteomalacic pattern that combines the features of osteoporosis with bone deformity. Soft-tissue ossification included involvement of ligaments, tendons, and interosseous membranes. RESULTS: Ninety-eight of the patients (89% of the adults) had some evidence of calcification and/or ossification of the attachments of ligaments, tendons, muscles, and interosseous membranes. Osteosclerosis was seen in 54 patients (43%), and osteopenia was seen in 51 patients (40%). Of the patients with osteopenia, the osteoporotic pattern was seen in 28 and the osteomalacic pattern in 23. Growth lines were found in 89 patients (70%). Metaphyseal osteomalacic zones were found in children. Diaphyseal widening was present in 35 patients (28%). CONCLUSION: Endemic skeletal fluorosis can have a wide variety of radiographic appearances, including calcification and/or ossification of the attachments of soft-tissue structures to bone, osteosclerosis, osteopenia, growth lines, and metaphyseal osteomalacic zones.

Adolescent↗
PubMed1995

Autosomal dominant osteopetrosis: bone mineral measurements of the entire skeleton of adults in two different subtypes.

Bone mineral content (BMC) and density (BMD) were measured by dual-energy X-ray absorptiometry in two subtypes of autosomal dominant osteopetrosis (ADO). Both types have been radiologically characterized by diffuse symmetrical osteosclerosis, but with characteristic differences. Increased thickness of the cranial vault is a typical finding in type I ADO, whereas endobones in the pelvis and end-plate thickening in the spine are obligate findings in type II. Eleven patients with type I from three kindreds, and seven patients with type II, one family participated in the study, and were compared with 18 age- and sex-matched normal controls. Whole-body BMC and BMD were measured, and regions of special interest were selected: head, axial, and appendicular skeleton. Moreover, lumbar spine and femoral neck scans were performed. Whole-body BMC and BMD, mostly reflecting cortical bone, were markedly increased in both types compared with normals. A pronounced osteosclerosis was present in the axial as well as the appendicular skeleton. Median BMD was markedly increased in the axial skeleton by 51% (44-56) and 42% (33-56), (median differences with 95% CI), respectively, for types I and II compared to normal controls, and in the appendicular skeleton by 48% (37-59) and 38% (16-45). No overlap between observed ranges of patients and controls was observed. A positive correlation between age and whole-body BMD was demonstrated in ADO, but not in the control group, indicating progressive osteosclerosis with age. Median BMD of the lumbar spine, which mostly reflects trabecular bone, showed increased densities in both types, 71% (51-84) and 59% (37-93), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed2004

Skeletal metastasis in patients with gastric cancer.

To clarify metastatic patterns, and histologic and radiologic features in skeletal metastases from gastric cancer, 48 patients were retrospectively analyzed. The mean age of the patients at the time of diagnosis of gastric cancer was 59 years. In 31 patients with a history of the radical surgery, the mean interval between surgery and diagnosis of skeletal metastasis was 14 months. The mean duration between diagnosis of skeletal metastasis and death was 60 days. Scintigraphic assessment showed that solitary osseous lesions were found in four patients, whereas the remaining 44 had multiple skeletal lesions. In 28 patients with bone-only metastases with absence of visceral metastases, a higher incidence of thoracolumbar metastases at the level nearest the stomach was found. The incidence of skeletal metastasis in each histologic type was intestinal in 19 and diffuse in 29. Radiologic examination revealed that the ratio between the presence and the absence of osteosclerosis was 1:2. Osteosclerosis was seen in three of 19 patients with intestinal type metastasis, whereas with the diffuse type 13 of 29 patients had osteosclerosis.

Adult↗
PubMed1991

Vertebral density distribution pattern: CT classification of patients undergoing maintenance hemodialysis.

The authors performed densitometry of the vertebral bodies in 152 patients undergoing renal hemodialysis and histologically examined four vertebrae from cadavers. Bone mineral density (BMD) values were found to be potentially misleading because the vertebrae are often heterogeneous, and the BMD value is merely an average value from one region of interest. To overcome this problem, the authors designed a computed tomographic classification that divides vertebral density distribution patterns into the following five types: normal (type 1), osteopenia (type 2), diffuse osteosclerosis (type 3), spotty osteosclerosis (type 4), and central osteosclerosis (type 5). This classification may be useful in the evaluation of bone changes in patients undergoing hemodialysis. The type 5 pattern is thought to be strongly related to secondary hyperparathyroidism and was often seen in younger patients and women. Many patients with aluminum-induced osteopathy had type 2 patterns, with decreased BMD in cortical bone.

Adult↗
PubMed1984

Bone histomorphometry in vitamin D-deficient rats infused with calcium and phosphorus.

Defective mineralization of bone and cartilage is the classical histological finding in vitamin D deficiency. Whether this represents a direct effect on mineral deposition or is a consequence of the decreased calcium and phosphorus levels that result from impaired intestinal absorption is not clear. A method has been developed in which vitamin D-deficient rats have plasma calcium and phosphorus levels maintained in the normal range by continuous infusion. Histomorphometric analysis of undecalcified tibiae from these animals was compared with that of rats given vitamin D. Epiphyseal growth plate thickness, trabecular osteoid volume, and mean osteoid seam width were not increased. Moreover, the administration of two time-spaced courses of tetracycline revealed that the mineralization rate and the time interval between apposition and subsequent mineralization of osteoid (mineralization lag time) were identical to those in rats treated with vitamin D. Trabecular bone volume was increased (osteosclerosis) in the vitamin D-deficient rats. In vitamin D-deficient controls without infusions, the osteosclerosis was mostly osteoid, whereas the excess bone was well mineralized in the vitamin D-deficient rats infused with calcium and phosphorus. Osteosclerosis in vitamin D-deficient animals may result from both decreased bone resorption and increased osteoid apposition. This study provides firm evidence that vitamin D is not essential for mineralization in young growing rats. Decreased availability of calcium and phosphorus thus may be the sole basis of the mineralization defect seen in vitamin D deficiency.

Animals↗
PubMed1995

Sclerosing IgA multiple myeloma.

A case of IgA multiple myeloma associated with myelofibrosis and radiological evidence of diffuse osteosclerosis from the disease onset is reported. Bone marrow trephine biopsies performed before and after chemotherapy treatment for myeloma showed grade 4 collagen fibrosis of the bone marrow, thickened bony trabeculae and the presence of plasma cells, both mature and immature. Serum electrophoresis revealed an IgA lambda-paraprotein. Throughout the course of the disease, there was persistent radiological evidence of osteosclerosis, although several lytic lesions appeared late in the disease process. The patient died 5 years after presentation, during an episode of septicaemic shock. It is speculated that cytokine(s) released by the neoplastic plasma cells may stimulate a fibroblastic reaction within the marrow, which subsequently undergoes bony metaplasia resulting in osteosclerosis.

Bone Marrow Examination↗
PubMed1995

Prognostic significance of bone metastasis from breast cancer.

There is no established method for assessing the prognosis of patients with breast cancer and metastasis confined initially to bone. The medical records of 82 patients with breast cancer nad metastasis confined initially to bone were reviewed. The following variables were analyzed at the time when bone metastasis was first diagnosed, to determine their relationship to length of survival: distribution of metastatic bone lesions on bone scan, presence of radiographic osteosclerosis in metastatic bone lesions, menstrual status, and disease-free interval. Univariate and multivariate analyses revealed that the distribution of metastatic bone lesions and the presence of radiographic osteosclerosis in these lesions were significant predictors of survival. Premenopausal or late postmenopausal status, and longer disease-free intervals (> or = 24 months) or no disease-free intervals (Stage IV breast cancer and metastasis confined to bone at the time of cancer diagnosis) showed a trend, although not statistically significant, toward longer survival. Distribution of metastatic bone lesions on bone scan and the presence of radiographic osteosclerosis in metastatic bone lesions should be considered prognostic variables for patients with breast cancer and metastasis confined initially to bone.

Adult↗
PubMed1993

Autosomal dominant osteopetrosis.

Autosomal dominant osteopetrosis is radiographically characterized by universal osteosclerosis, primarily involving the axial skeleton, and by symmetrical affections of the long bones without modeling defects. Based on standard radiographs, it is possible to describe two different subtypes with different clinical, biochemical, and histologic manifestations. Type I is radiographically characterized by pronounced osteosclerosis of the cranial vault, whereas Type II has end-plate thickening of the vertebrae (Rugger-Jersey spine) and endobones in the pelvis. Both types are strictly family related and seen in childhood. Combined radiogrammetric, biochemical, and histologic investigations indicate states of defective bone resorption, whereas bone formation seems to be normal in both types of patients. Patients with autosomal dominant osteopetrosis are often asymptomatic, and the diagnosis may be reached by chance. However, by systematic investigations, nearly all patients have manifestations related to the disorder. Symptoms are progressive with age, and correlated with osteosclerosis. The fracture frequency is increased in Type II patients, and normal in Type I, where biomechanical investigations have shown normal, or even increased trabecular bone strength. Treatment has been symptomatic. A rational treatment consists of stimulation of bone resorption, in combination with inhibition of bone formation if possible.

Bone Resorption↗
PubMed1996

[Roentgenological and histomorphological studies of the knee joint in rheumatoid arthritis].

In order to study the disease process of rheumatoid arthritis in the knee joint, clinical and roentgenological analysis as well as histomorphological study of the proximal tibia taken at total knee arthroplasty procedure were carried out. The natural course of eight patients who had been followed 12.7 years on an average were studied in respect to range of motion, swelling, pain, instability of the knee joints along with radiographical appearance of the knee joints and other locations such as hand, spine and other major joints. There were two extreme types: one which led to obvious joint instability and one which ended up with joint contracture. The majority of the cases, however, fell between the two types. These three groups well corresponded to the three types proposed earlier by Katsube: unstable, stiff and standard types, respectively. For the roentgenological analysis, 148 knees of 80 preoperative patients were also subjected. The findings included osteoporosis, abnormal femoro-tibial angle, osteophyte formation, bone destruction with or without osteosclerosis. There were apparent bone destruction and a tendency toward valgus demormity in the unstable type, whereas apparent osteoporosis and little osteosclerosis of the tibial plateau were found in the stiff type. In the standard type, there were osteophyte formation and osteosclerosis of the tibial plateau as usually seen in osteoarthritic knees. For the histomorphological study, 30 patients were given tetracycline hydrochloride preoperatively for tetracycline labeling and total of 38 knees were thus examined. The specific findings in the unstable type included severe pannus formation and bone absorption, and those in the stiff type were severe osteoporosis with articular cartilage degeneration and decreased mineralization. No specific findings were observed in the standard type.

Adult↗
PubMed1992

Case report 705. Osteosclerotic sarcoidosis.

In summary, Sarcoidosis is a rare but well-recognized cause of diffuse osteosclerosis. The differential diagnosis of osteosclerosis is limited and includes osteoblastic metastases, sclerotic myeloma, myelofibrosis, and less common infiltrative bone marrow processes such as mastocytosis and sarcoidosis. In all of these entities the sclerosis is found most often in the axial (red marrow) skeleton. In this regard, it is interesting that cases of osseous sarcoid are usually lytic and located in the peripheral skeleton. In patients with osteosclerotic sarcoidosis, the diagnosis may be suggested by a past history of the disease or ancillary signs such as hilar node enlargement and subtle skin involvement. However, the specific diagnosis usually requires bone marrow biopsy with the demonstration of extensive, noncaseating granulomas.

Bone Diseases↗
PubMed1989

Osteomesopyknosis. Report of two new cases.

Two inherited cases of osteomesopyknosis are reported. This is an autosomal dominant osteosclerosis described by Maroteaux in 1980; its radiological abnormalities consist of increased density of the vertebral plates, pelvis, and sometimes of the upper part of the femur. Osteomesopyknosis, usually discovered incidentally on radiographic examination, is a mild form of familial osteosclerosis and must be distinguished from osteopetrosis which carries a worse prognosis.

Adolescent↗
PubMed1989

Histomorphometry of bone marrow biopsies in primary osteomyelofibrosis/-sclerosis (agnogenic myeloid metaplasia)--correlations between clinical and morphological features.

Histomorphometry was performed on representative trephine biopsies of the bone marrow on admission of 50 patients (21 male, 29 female - age 67 years) with so-called primary osteomyelofibrosis/-sclerosis (OMF) not preceded by any other subtype of chronic myeloproliferative disorders. This study was firstly aimed at testing correlations between histological features (amount of haematopoiesis, cytological aspects of megakaryocytes, density of reticulin and collagen fibres and degree of osteosclerosis) and laboratory data, as well as spleen size and duration of relevant prediagnostic symptoms. Secondly, we concentrated on a discrimination of OMF patients into two subgroups according to bone marrow morphology and clinical variables. Statistical evaluation of histomorphometric variables and haematological findings disclosed that there was a progressive fibro-osteosclerotic process in the evolution of disease features. Increase in medullary fibrosis was significantly paralleled by an abnormal or pleomorphic megakaryopoiesis in the bone marrow: there was an increase in irregularity of perimeters for megakaryocytes and naked nuclei combined with smaller sizes of these elements including the nuclei. Additionally, there was a greater number of pycnotic bare nuclei. A number of morphometric features (density of fibres, degree of osteosclerosis, amount of haematopoiesis) were associated with corresponding clinical data (spleen size, length of preclinical history). By consideration of a set of basic histomorphometric variables our cohort of 50 patients could be divided into an early hyperplastic subtype with no or minimal medullary reticulin and another group with conspicuous fibrotic and osteosclerotic alterations of the bone marrow. It was noticeable that we found no significant correlation between amount of haematopoiesis or marrow cellularity with splenomegaly. This result suggests that splenic haematopoiesis (myeloid metaplasia) may represent an autonomous or neoplastic process and not only compensation for a failing fibro-osteosclerotic bone marrow.

Aged↗