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The literature contains little reference to the phenomenon of osteosclerosis in leprosy. The aim of the authors' investigations was to determine: a) the incidence of osteosclerosis as part of the radiographic picture in the distal extremities of the limbs; b) the pathological substratum; c) the possible clinical significance. The research was carried out on 233 leprosy patients at the Colonia Hanseniana di Gioia del Colle (Bari). The authors examined 260 radiographs of the hands and 1310 radiographs of the feet. A number of biopsy samples of bone were taken from four patients and examined by means of microradiography using ultraviolet fluorescent light and also by historadiography. The basic radiographic features indicative of osteosclerosis were: a) reactive osteosclerosis; b) sclerosing periostosis; c) massive osteosclerosis. The authors observed a preponderance of osteosclerosis in the bones of the first digital ray, both in the phalanges and metatarsals or metacarpals. The sesamoid bones were affected more commonly in those of the first digit than those of the fifth. The radiographic findings were confirmed microscopically. It is difficult to assess the possible clinical significance because of the transient nature of the osteosclerosis in the evolution of the lepromatous lesions with time.
Six out of 30 patients with chronic renal failure showed osteosclerosis in the lateral radiograph of the lumbar spine. When two groups with a similar degree of renal impairment were compared, the patients with osteosclerosis were younger and had a significantly higher level of circulating PTH (p less than 0.05) and total hydroxyproline excretion (p less than 0.02), than patients without overt osteosclerosis. The metacarpal cortical thickness was significantly reduced in patients with vertebral osteosclerosis. The results suggest that in patients with chronic uremia endogenous hypersecretion of PTH is one of the most significant factors responsible for the development of osteosclerosis. The mineral released from other skeletal sites could be utilized in the mineralization of the newly formed trabecular bone without any external calcium gain.
Myelofibrosis and osteosclerosis are prominent features arising in mice overexpressing thrombopoietin (TPO). The pivotal role of transforming growth factor beta 1 (TGF-beta 1) in the pathogenesis of myelofibrosis has been documented, but the mechanisms mediating osteosclerosis remain unclear. Here, we used mice deficient in osteoprotegerin (OPG), a secreted inhibitor of bone resorption, to determine whether osteosclerosis occurs through a deregulation of osteoclastogenesis. Marrow cells from opg-deficient mice (opg(-/-)) or wild-type (WT) littermates were infected with a retrovirus encoding TPO and engrafted into an opg(-/-) or WT background for long-term reconstitution. The 4 combinations of graft/host (WT/WT, opg(-/-)/opg(-/-), opg(-/-)/WT, and WT/opg(-/-)) were studied. Elevation of TPO and TGF-beta 1 levels in plasma was similar in the 4 experimental groups and all the mice developed a similar myeloproliferative syndrome associated with severe myelofibrosis. Osteosclerosis developed in WT hosts engrafted with WT or opg(-/-) hematopoietic cells and was associated with increased OPG levels in plasma and decreased osteoclastogenesis. In contrast, opg(-/-) hosts exhibited an osteoporotic phenotype and a growth of bone trabeculae was rarely seen. These findings suggest that osteosclerosis in mice with TPO overexpression occurs predominantly via an up-regulation of OPG in host stromal cells leading to disruption of osteoclastogenesis.
OBJECTIVE: Osteosclerosis of the terminal phalanges of the hand has been reported in the collagen diseases including rheumatoid arthritis (RA). The current study was made to clarify the significance of terminal phalangeal osteosclerosis in RA. METHODS: Hand x-ray films of 108 patients (male 13, female 95) with RA for more than 10 years were assessed by Halim's grading. Grade 2, (Distance between both cortices is < 1 mm but there is still an intermediate space discernible), and grade 3, (Complete fusion of both cortices, but the base of the terminal phalanx is open), were classified as the positive group. Grades 0 and 1 were classified as the negative group. Both groups were compared and sigma GS/D values was measured at terminal phalanges, middle phalanges and metacarpuses of right middle fingers using digital image processing method. sigma GS/D index was calculated as being equal to the ratio of sigma GS/D value of the terminal or middle phalanx to sigma GS/D value of the metacarpus. RESULTS: Thirty cases (28%) were positive (male 1, female 29). Osteosclerosis of terminal phalanges usually appeared in more than two digits bilaterally. It was located as follows; thumb-1 case, index-13 cases, middle-24 cases, ring-51 cases, little-58 cases. Obliteration of the medullary space of middle phalanges was seen in 5 cases. No difference was observed between the positive and negative groups about sex, age, the mean value of C-reactive protein, the incidence of Steinblocker's class classification and the rate of seropositive patients. Osteosclerosis of terminal phalanges was observed at first consultation in 93% of positive cases. Osteosclerosis is expected to appear in the early phase of RA and to last for more than 10 years. sigma GS/D index of the positive group (1.03 +/- 0.24, mean +/- SD) was greater than that of the negative group (0.63 +/- 0.25) (p < 0.05).
Standardized panoramic radiographs were used to determine and compare the prevalences of focal osteosclerosis (including condensing osteitis) and apical periodontal pathoses in a sequential presenting sample of 600 European and 600 Cape Coloured dental outpatients. Most cases of focal osteosclerosis were found in edentulous zones or associated with carious or inadequately restored teeth; however, some were subjacent to apparently sound teeth. Focal osteosclerosis of definite dental origin was just as common in participants aged 25 years and older as in younger individuals. While focal osteosclerosis occurred predominantly in the mandible, apical periodontal pathoses were distributed more evenly between both jaws.
OBJECTIVE: The purpose of this study was to determine the frequency and anatomic location of idiopathic osteosclerosis in the jawbones and to present computed tomographic findings of this lesion in Japanese patients. STUDY DESIGN: Panoramic radiographs of 1047 patients were examined for the presence of idiopathic osteosclerosis in the jawbones. Computed tomography was performed in 11 patients of this series. RESULTS: A total of 64 patients (6.1%) showed this radiopacity. The highest occurrence was in the mandibular first molar region. There was no statistically significant difference in the prevalence of idiopathic osteosclerosis between males and females. On computed tomography images, these radiopaque areas were divisible into two types: enostosis (five cases) and central sclerosis (six cases). CONCLUSION: This is the first report of computed tomographic findings on idiopathic osteosclerosis in the jawbones, although the results on panoramic radiographs are similar to other investigators.
AIM: To compare the prevalence of idiopathic osteosclerosis in the jaws in Hong Kong and Britain. METHODS: The panoramic radiographs of consecutive patients who attended the primary care departments of the dental hospitals in Hong Kong in 1981 and 1990 and London in 1990 and of Edinburgh in 1993 were reviewed. The size of the Hong Kong lesions was measured. The literature was subjected to systematic review. RESULTS: The prevalence of idiopathic osteosclerosis in Hong Kong in 1981 and 1990, London and Edinburgh was 6.7, 5.5, 2.7 and 4.1% respectively. The prevalence of idiopathic osteosclerosis was greater in the Oriental (Chinese and Japanese) than in Western surveys. The lesions in the 1990 Hong Kong survey in the third decade were significantly smaller than those in the 1981 survey. The decrease in size in Hong Kong 1990 was also accompanied by a reduction in overall prevalence. The predilection for the mandible, especially in the premolar area, was observed in the Chinese and London series; this feature was also common to all other reports. CONCLUSION: The Chinese have a greater prevalence of idiopathic osteosclerosis than Western populations.
Autosomal dominant osteosclerosis, an entity previously labelled by various names, is clearly separate from Van Buchem disease; Van Buchem disease exhibits autosomal recessive inheritance. The clinical manifestation of autosomal dominant osteosclerosis is a widened and deepened mandible with increased gonial angle. Radiographic manifestations include endosteal sclerosis of the neurocranium with loss of the diploë, osteosclerosis and hyperostosis of the mandible with absence of the normal antegonial notches, endosteal sclerosis of the diaphyses of long bones (including metacarpals and metatarsals), and osteosclerosis of the pelvis.
We studied a family with autosomal dominant osteosclerosis associated with familial spinal canal stenosis. The propositus, a 44-year-old Japanese woman, had a 9-month history of occipitalgia and left tinnitus, and also had a 2-month history of pain and numbness of the right upper limb. Radiographic skeletal survey showed osteosclerotic changes in the neurocranium, diaphysis of the long bone, mandible, shoulder, clavicle, and ribs. Serum alkaline phosphatase was normal, and no periosteal excrescences were seen. The inheritance pattern was autosomal dominant. The propositus and her daughter, both with severe osteosclerosis, showed spinal canal stenosis, but her son, whose osteosclerosis was moderate, did not. This is the first report of autosomal dominant osteosclerosis associated with familial spinal canal stenosis.
Osteosclerosis of the subchondral bone was measured by densitometer on plain radiographs in 55 medial compartmental osteoarthritic knees of 40 patients who were treated with high tibial valgus osteotomy for correction of varus deformity. The ratio of the osteosclerosis value of the medial side of the knee to that of the lateral side (Medial/Lateral ratio) was calculated and used as a parameter. The Medial/Lateral ratio of osteosclerosis decreased rapidly within three years after osteotomy at the reference points of the femur and the tibia. Even 7 to 19 years after osteotomy, a decrease of the ratio was noted in 16 knees with a standing femorotibial angle (FTA) less than 168 degrees (12 degrees of anatomical valgus angulation). This was interpreted to mean that osteosclerosis of the medial condyle decreased compared with that of the lateral condyle after overcorrection of varus deformity. In the cases of more than 7 years after high tibial osteotomy, a positive straight regression line was drawn by calculation between Medial/Lateral ratio and postoperative limb alignment expressed by standing femorotibial angle, with coefficient of correlation (gamma) of 0.295 (p < 0.01).
Osteosclerosis of the subchondral bone was measured by densitometry on plain roentgenograms in 55 medial compartmental osteoarthritic knees of 40 patients who underwent high tibial osteotomy for correction of varus deformity. The osteosclerosis value of the medial side of the knee to that of the lateral side (Medial/Lateral ratio) was calculated and used as a parameter. Medial/Lateral ratios of the osteosclerosis were increased from 0.90 +/- 0.15 preoperatively to 0.99 +/- 0.20 (p < 0.05) postoperatively in 2 mm proximal area from the joint surface of the femur, from 0.95 +/- 0.15 to 1.04 +/- 0.21 (p < 0.05) in 7 mm proximal area from the joint surface of the femur, and from 0.87 +/- 0.14 to 0.95 +/- 0.13 (p < 0.05) in 2 mm distal area from the joint surface of the tibia within 3 years. The increase of the ratio was noted more than 7 years after osteotomy in the cases with standing femoro-tibial angle (FTA) less than 165 degrees. This is interpreted to mean that osteosclerosis of the medial chondyle decreased as compared with that of the lateral condyle after correction of varus deformity. More than 7 years after high tibial osteotomy, minus straight line relationship was found between Medial/Lateral ratio and FTA in 2 mm proximal area from the joint surface of the femur of the case with FTA less than 175 degrees with coefficient of correlation -0.408 (p < 0.05) and in 2 mm distal area from the joint surface of the tibia with coefficient of correlation -0.437 (p < 0.01). From these results, the sufficient correction of varus deformity is considered to be one of the most important factor in the treatment of osteoarthritis of the knee.
We have previously shown that mice induced to overexpress thrombopoietin (TPO) by retroviral-mediated gene transfer into bone marrow (BM) cells develop myelofibrosis and osteosclerosis. It was speculated that these effects were secondary to TPO, resulting from high levels of megakaryocytes and platelets. Also, it was proposed that these mice represent a model for myelofibrosis and osteosclerosis. In this report, we show that levels of both transforming growth factor-beta 1 and platelet-derived growth factor are increased twofold to fivefold in the platelet-poor plasma of TPO overexpressing mice compared with control mice. These data suggest that the increased megakaryocytes produce elevated levels of these cytokines that lead to the pathogenesis of disease. Further, we retransplanted TPO overexpressing mice, at 40 to 42 weeks after primary transplantation, with normal BM cells. After the secondary transplantation, megakaryocytes and platelets returned to normal levels and the myelofibrosis and osteosclerosis were completely corrected. These data extend our initial studies of the effects of overexpression of TPO and show the potential use of this model to explore the underlying cause of myelofibrosis and osteosclerosis and potential treatments for these diseases.
IBIDS is a syndrome characterized by ichthyosis, brittle hair, impaired intelligence, decreased fertility, and short stature, but unassociated with skeletal lesions. This condition is considered a form of trichothiodystrophy because hair from several cases has been found to have a low sulfur content. We describe a 9-year and 10-month-old white boy whose clinical features resemble the IBIDS syndrome (ichthyosis, brittle hair, cataracts, and short stature), but who also has marked axial osteosclerosis and peripheral osteopenia. No abnormalities of mineral homeostasis were noted. Histopathologic assessment of nondecalcified bone specimens excluded osteopetrosis, but suggested slow skeletal remodeling. When subjected to polarized light microscopy, his hair exhibited the band-like pattern of birefringence described in trichothiodystrophy. Literature review disclosed 8 patients, 2 of whom had been diagnosed as trichothiodystrophy, with like clinical features including osteosclerosis. These skeletal abnormalities together with clinical features of the IBIDS/trichiodystrophy syndrome, we believe, reflect the prototype of a disorder that seems best described as central osteosclerosis with ectodermal dysplasia.
A former intravenous substance abuser, seropositive for hepatitis C virus infection, was referred for diffuse osteosclerosis. There was no history of fracture or skeletal deformity. Cortical and trabecular bone density was approximately twice the mean value for controls. Skeletal histology revealed dense lamellar bone. Recognized causes of acquired generalized osteosclerosis or hyperostosis were excluded. This patient verifies the syndrome of painful diffuse osteosclerosis after intravenous drug abuse and shows that skeletal mass can be markedly increased with histologically normal, structurally sound bone during adult life. Elucidation of the etiology and pathogenesis could offer an effective treatment for osteoporosis.
PURPOSE: We identify a new syndrome of acquired painful diffuse osteosclerosis associated with past intravenous drug abuse in two adults. METHODS: A 28-year-old white woman and a 38-year-old black man with a history of non-A, non-B chronic active hepatitis were referred to us for increasing bone pain that was especially severe in their lower extremities. They were studied at our clinical research center. RESULTS: Skeletal radiographs documented progressive generalized osteosclerosis. Increased bone mass was confirmed by dual-energy radiography, and bone scintigraphy showed diffusely increased radionuclide accumulation. Serum biochemical studies revealed elevated alkaline phosphatase activity and osteocalcin levels, mild to moderately increased 1,25-dihydroxyvitamin D concentrations, and normal parathyroid hormone levels. In urine, hydroxyproline excretion was elevated, whereas calcium levels were reduced. Iliac crest histomorphometry showed increased rates of bone formation. Hematology, renal function, serum protein electrophoresis, and screening for fluorosis as well as vitamin A and heavy metal poisoning were all normal. Family histories were negative. Both patients were seropositive for antibody against hepatitis C virus as well as against Epstein-Barr virus (antiviral capsid antigen IgG but not IgM). Each subject was seronegative for cytomegalovirus, human immunodeficiency virus (HIV) 1 and 2, and human T-cell lymphotropic virus (HTLV) 1 and 2. Assay for reverse transcriptase in lymphocyte co-culture fluid and polymerase chain reaction studies using HIV-1 primers on peripheral monocyte DNA were negative. Treatment with synthetic salmon calcitonin in both individuals rapidly led to decreased bone pain and to a decline in biochemical parameters of accelerated bone turnover. CONCLUSION: Painful diffuse osteosclerosis can follow intravenous drug abuse and is possibly caused by parenteral transmission of a virus that in some way stimulates bone formation.