Bone Manifestations Research Articles

Brucelosis en un escolar

We describe the case of a student with a history of two and a half months of fever, hepatosplenomegaly, cutaneous, hematological and bone manifestations, within an epidemiological background compatible with the diagnosis of Brucellosis. Diagnosis of Brucella abortus was confirmed by serology and positive blood cultures. Clinical manifestations of brucellosis and diagnostic and treatment strategies are reviewed.

The relationship between nail- and distal phalangeal bone involvement severity in patients with psoriasis

We aimed to investigate the relationship between nail involvement and joint manifestations and whether there was a correlation between nail psoriasis severity and bone manifestations in psoriatic patients without symptomatic psoriatic arthritis in plaque type psoriasis. Thirty-one patients with nail involvement (16 men, 15 women, mean age 45.29+/-18.73) and 39 patients without nail involvement (16 men, 23 women, mean age 38.41+/-17.33) were enrolled in the study. X-ray of the hands and feet with magnification were performed. The distal interphalangeal (DIP) joint and bone (tuft of terminal phalanx) were evaluated. A scoring method was performed on the patients with nail involvement. There was no difference in DIP joint involvement in patients with or without finger- and toenail involvement (p=0.085 and p=0.062, respectively). However, the prevalence of bone involvement was higher in patients with finger- and toenail involvement than without finger- and toenail involvement (p=0.039 and p=0.021, respectively). A positive correlation was also determined between finger- and toenail psoriasis severity and bone involvement severity (r=0.379, p=0.001 and r=0.288, p=0.015).

Hyperactivation of p21ras and PI3-K Cooperate To Alter Murine and Human NF1 Haploinsufficient Osteoclast Functions.

Neurofibromatosis type 1 (NF1) is a common genetic disorder caused by mutations of the NF1 tumor suppressor gene that functions as a GTPase activating protein for Ras. Though nullizygous loss of NF1 is associated with the development of malignancies, haploinsufficient phenotypes are now being increasingly recognized to alter cell fates and functions in a number of tissues resulting in nonmalignant disease manifestations. Bone manifestations, including skeletal dysplasias, scoliosis, and osteoporosis occur in 30–60% of all NF1 patients and osteoporosis is an increasingly recognized health problem for women with NF1. However, understanding of the cellular and molecular basis of these sequelae is incomplete. Osteoclasts are specialized myeloid cells that are the principal bone resorbing cells of the skeleton. Using an established murine model of NF1 developed using homologous recombination, we found that Nf1+/− mice contain elevated numbers of multinucleated osteoclasts and osteoclast progenitors per femur in vivo. Both osteoclasts and osteoclast progenitors from Nf1+/− mice were hyperresponsive to limiting concentrations of M-CSF and RANKL, growth factors that are integral to osteoclast maturation and activation. M-CSF stimulated p21ras-GTP and Akt phosphorylation was elevated in Nf1+/− osteoclasts associated with gains in function in survival and proliferation. Bone resorption by osteoclasts is linked to the migration and adherence of these cells to a local bone surface. Purified populations of Nf1+/− osteoclasts were initially placed in the upper chamber of a transwell coated with vitronectin and haptotaxis to M-CSF was determined. Nf1+/− osteoclasts had a 2–3 fold increase in migration as compared to syngeneic wildtype cells. A similar increase in adhesion of Nf1+/− osteoclasts to the integrin avb3 was also observed. Following adhesion, osteoclasts form a specialized cell-extracellular matrix to initiate degradation of bone matrix by secreting proteinases. Nf1+/− osteoclasts had significantly increased bone resorption as measured by scoring the number and area of individual bone resorbing “pits” on dentine slices and by scoring the total area of resorption. These collective increases in osteoclast function were validated in vivo by the observation that serum TRAP5b activity, a sensitive measure of osteoclast lytic activity was 2.5 fold higher in Nf1+/− mice as compared to WT mice. Furthermore, we performed ovariectomy, an established model of osteoporosis associated with an increase in osteoclast function. In two independent experiments, we found that Nf1+/− mice had a significantly greater reduction in bone mineral density following ovariectomy as compared to syngeneic wildtype mice. We hypothesized that hyperactivation of class1A-PI3-K may contribute to these gains in cellular function. We found that intercrossing Nf1+/− and Class1A PI3-K deficient mice (p85a) restores elevated PI3-K activity, and Nf1+/− osteoclast functions to wildtype levels. Furthermore, in vitro differentiated osteoclasts from NF1 patients also display elevated Ras-PI3-K activity and increased lytic activity analogous to murine Nf1+/− osteoclasts. Collectively, we identify a novel cellular and biochemical NF1 haploinsufficient phenotype in osteoclasts that has potential implications in the pathogenesis of NF1 bone disease.

Monoclonal Gammopathy (MG) Associated with Gaucher Disease (GD). Report of 16 Cases from the French Observatoire on Gaucher Disease (FROG Study).

In addition to its common bone and visceral manifestations GD is frequently associated with B cell proliferation leading possibly to MG. The objective of our study was to determine the frequency and presentation of MG in GD patients.Material and methods. FROG is a cross-sectionnal epidemiological study on adult GD involving 64 French centers. Standard clinical, biological(including serum protein electrophoresis) and imaging data performed as part of usual management within the 3 previous years were collected at the time of a routine visit. In patients with suspected MG specific additionnal data were studied:immunofixation, dosage of immunoglobulins, bone marrow aspiration.Results. From 05/2005 to 06/2006 seventy seven adult GD type 1(38 male,39 female;mean age 47.3 years, range 18 to 78 years) were included. Sixteen cases of MG(20.8%) were observed (10 male and 6 female;mean age 61.25 years, range 47 to 79 years). Mean age of 61 cases of GD without MG(43.8 years;range 18 to 70 years)was significantly lower(p<0.0001). Thirteen cases(17%)were classified as MGUS and 3 (3.8%) as B cell malignancy:1 multiple myeloma, 1 Chronic Lymphocytic Leukemia, 1 Non Hodgkin Lymphoma. In 3 cases MG and GD were diagnosed simultaneously. In 13 cases MG was diagnosed in the course of GD(mean interval 12.2 years;range 6.7 to 16 years). MG immunochemical typing revealed 75 % Ig G, 12.5 %Ig A, 12.5 %Ig M, 75 % Kappa and 25 % Lambda. We observed one biclonal gammopathy(IgG and IgA Kappa). One case of MGUS was associated with capillary leak syndrome. In two patients MG level decreased with enzyme replacement therapy.Conclusion. Frequency of MG in GD observed in our study (20.8%)is largely higher than in general population (1%). Furthermore this frequency is higher than in previous series of GD. However in GD patients, as observed in general population, frequency of MG seems to be related to age as mean age of patients with MG is significantly higher than mean age of patients without MG. Finally these data assess the need of specific follow-up regarding the high frequency of MG and the risk of B cell malignancy in GD patients.

Variation of Serum Lipid Profile during Enzyme Replacement Therapy, in Patients with Type 1 Gauchers Disease.

Enzyme Replacement Therapy (ERT) has dramatically changed the clinical course and prognosis of patients with Gaucher disease. We have assessed the extent to which the recently defined Goals of Therapy (Pastores et al, Semin Hematol 41(suppl 5):4–14) in 9 major fields (anemia, thrombocytopenia, hepatomegaly, splenomegaly, skeletal pathology,biomarkers, pulmonary manifestations, growth and functional health and well being) were achieved in our cohort of patients with type I Gaucher disease. Fifty-seven patients (27 females, 30 males, median age at diagnosis 30 years (range 2–77 years) and at start of ERT 39 years (range 5–79 years) were assessed. The median period of ERT was 94 months (range 24–155 months). Patients on ERT for less than 2 years were excluded. Twenty five specific goals are defined within the 9 fields. The median overall success rate was 20 of 25 goals or 80% per patient (range 12–25 goals or 60–100%). The success rate for 9 goals was 100% ( normalization of hemoglobin 1 year post-splenectomy, no major bleeding 1 year after ERT start, doubling of baseline platelet count in severely thrombocytopenic patients 2 years after ERT start, maintenance of platelet count in non-thrombocytopenic patients, prevention of bone crises, reversion of hepatopulmonary syndrome and dependence on oxygen, amelioration of pulmonary hypertension and prevention of rapid deterioration of pulmonary disease and sudden death). Higher success rates were achieved for the goals related to thrombocytopenia (97.9%) and pulmonary manifestations (97%) although in the latter case the applicability was low. Lower success rates were achieved for the goals related to bone manifestations (78.7%). There was no significant difference in the success rate between males and females, splenectomised and non-splenectomised patients, and between patients treated less or more than 6 years. However patients started on ERT before the 40th year of age exhibited significantly higher success rate as compared to patients started after the 40th year (p=0.047) and there was a significant inverse correlation between overall success rate and patient's age at treatment start (r = − 0.437). Finally, the success rate was higher among double heterozygotes, carrying the N370S mutation, as compared to patients homozygous for the N370S mutation (89.2±9.6% vs. 80.2±12.9%, p=0.016).

Les manifestations neurologiques de la maladie de Gaucher de type 1 : vers une remise en cause de la classification actuelle ?

Gaucher's disease (GD), the most prevalent inherited lysosomal storage disorder, is caused by deficient glucocerebrosidase activity. The resulting accumulation of glucocerebrosides in lysosomes of macrophages leads to hepatosplenomegaly, anemia, thrombocytopenia, and various bone manifestations. Gaucher's disease is classified into 3 types based on the nature of its effects on the central nervous system. Type 1, the most common variant, is classically nonneuronopathic. However, the occurrence of Parkinsonism seems to be more frequent in type I Gaucher's disease than in the general population. Furthermore, heterozygotes for certain glucocerebrosidase gene mutations have a higher risk to develop Parkinson's disease. We report our experience about 9 patients with Gaucher's disease and their association with neurological manifestations. These recent data may discuss Gaucher's classification and the existence of a continuum between neurologic and non-neurologic forms of the disease.

OC5 Diagnosis of secondary syphilis due to oral lesions

Syphilis is a sexually transmitted disease caused by Treponema pallidum that typically produces skin and oral lesions during the acute phase. In the chronic phase, bone, viscera, cardiovascular, and neurological manifestations may appear. Therefore, syphilis is classically divided into stages of occurrence, with each stage having its own peculiar signs and symptoms related to time and antigen‐antibody responses. The stages are primary, secondary, latent, tertiary, and congenital. Oral lesions of secondary syphilis are rare, however, they may present and the dentist should be able to diagnose them. A 23‐years‐old white male was referred by his physician to our clinic. The oral mucosa presented several irregular, shallow ulcers, with definite limits and variable shape. Additional ulcers and red macular lesions were present in the tongue, palate and labial mucosa. In the anamnesis, the patient reported having previously palm‐plantar papule‐macular red lesions. Physical examination revealed no cervical or submandibular lymphadenopathy and no facial asymmetry. The patient noted that the painful, vesicular and ulcerated lesions appeared one month ago. In that moment, he also presented with asthenia, dysphagia and pain. Routine hematologic examination was normal. The patient's medical history was insignificant except for an episode of urethritis six months before. He had been treated by his physician with topical corticoids, with no favourable improvement of lesions. His medical history and clinical features were consistent with secondary luetic disease. Serologic studies supported this diagnosis. The syphilis was treated with penicillin G, with complete remission of the lesions.

Bone manifestations of actinomycosis

Actinomycosis, originally classified as a fungus, is now considered a branching bacteria. Although jaw involvement often presents with classic pathognomonic signs, postcranial disease has not been so characterized. Affected bones from individuals diagnosed in life with actinomycosis were macroscopically and radiologically examined for their macroscopic character. The bones were riddled with spheroid, occasionally coalescing defects associated with periosteal reaction. Erosion penetrated cortical bone as readily as through cortical bone or subchondral bone. X-ray revealed circular lesions with a slight sclerotic margin. Actinomycosis apparently has unique features, which should allow it to be distinguished from multiple myeloma (because of presence of reactive new bone formation) and from fungal disease (because of lack of "fronts of resorption" and penetrating spicules). Similarity to fungal infection is especially of interest because of the earlier phylogenetic classification question.

In SAPHO syndrome anti-TNF-α therapy may induce persistent amelioration of osteoarticular complaints, but may exacerbate cutaneous manifestations

SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteitis) is a rare disease combining skin, bone and joint manifestations. In recent years new therapeutic strategies have been tried, among them TNF-alpha-blocking agents. We report our experience with infliximab in four cases of SAPHO syndrome refractory to conventional therapies. Between 2002 and 2005, four cases of SAPHO syndrome (two females and two males; mean age 49.7 yr) responding poorly to conventional drugs were treated with infliximab. The dose was 5 mg/kg, according to the protocol used in spondyloarthropathies, with infusions at 0, 2 and 6 weeks followed by 6 weeks intervals. No active cutaneous manifestations were present at the time of starting therapy. Complete remission of osteoarticular involvement was achieved after the second or third infusion, and the positive response was maintained for up to 12 months. A patient relapsed after discontinuation of infliximab, because of infectious complication. Palmoplantaris pustulosis relapsed in two patients after three and six infusions, respectively; there was slight improvement after discontinuation of anti-TNF-alpha drugs. Infliximab seems to be a very effective therapy for osteoarticular complaints of SAPHO syndrome. Cutaneous involvement responded less favourably, palmoplantaris pustulosis relapse being a possible complication.

Primary hyperparathyroidism: 7,000 years of progress.

Because of widespread screening of the serum calcium concentration, most patients with primary hyperparathyroidism now present with very mild disease instead of the severe bone or kidney manifestations seen in the past. The US National Institutes of Health (NIH) in their 2002 guidelines recommend surgery for patients with symptoms and for select patients without symptoms. But many now argue that all patients with primary hyperparathyroidism should be referred for surgery to reduce fracture risk and enhance general health.

Skeletal manifestations of infantile scurvy

Recent investigations of human skeletal material from the historic St. Martin's cemetery, England, found a range of abnormal lesions in six infants that are almost certainly related to scurvy. Porous and proliferative bone lesions affecting the cranial bones and scapulae were found, and this paper presents images obtained using both macroscopic and scanning electron microscope examination of the lesions. Previous work on infantile scurvy (Ortner et al., 1997-2001) relied heavily on changes at the sphenoid, which is often missing in archaeological bone, so the identification of changes attributable to scurvy on other cranial bones and the scapulae is encouraging. The ability to recognize changes related to scurvy on a range of bones will ensure an enhanced potential for recognition of this disease in future research involving archaeological bone. Research on historical documents from Birmingham dating to the eighteenth and nineteenth centuries, combined with the probable cases of scurvy identified, supports the view that the paucity of cases of infantile scurvy from the archaeological record reflects a lack of understanding and recognition of bone manifestations, rather than a lack of occurrence in this period. Changes linked to scurvy were only found in infants from the poorer sections of the community from St. Martin's, and this is almost certainly linked to patterns of food consumption and may be related to shortages of potatoes, due to blight, experienced during this period.

Manifestations ostéoarticulaires des anémies

Osteoarticular manifestations due to haemolytic anaemia are not rare. Generally, they appear early in childhood but they may remain causing great problems of management in adulthood and, thus, concern the rheumatologist. During the management of thalassaemia, various painful bone or joint manifestations may be encountered. Osteoporosis has become a more frequent disorder due to the lengthening of survival that has resulted from an improved therapeutic management. Biophosphonates have shown efficacy in significantly increasing the bone mass. The principal complication of beta-thalassaemias is the vaso-occlusive attack that, at the bone level, may be responsible for bone infarct or aseptic osteonecrosis. Other painful manifestations may be observed, such as septic arthritis or aseptic arthropathies. In such cases also, multidisciplinary management allowed reducing mortality and improving survival.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome in a 14-year-old boy: an immunohistochemical study of infiltrating lymphocytes in acneous skin regions

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome was proposed as a clinico-radiological entity combining skin, bone and joint manifestations [1]. Here, we report a 14-year-old boy with SAPHO syndrome, in whom we investigated the pathology of acneous skin regions with aberrant T-cell lymphocyte infiltration in the dermal area. A 14-year-old boy was admitted to our hospital exhibiting persistent high-grade fever with acne conglobata, in addition to chest, left knee joint and lumbar pain. Physical examination revealed swelling of the left knee joint and severe facial acne (Fig. 1). Haematological and biochemical investigations were all normal; however, C-reactive protein was 8.58 mg/dl and the ESR was 54 mm/h. Urinalysis showed normal findings. The purified protein derivative of tuberculosis reaction was unchanged from the previous year. Blood, urine, stool and pharyngeal cultures were all negative. Compliment, ferritin, and serum immunoglobulin level were normal. LE test, antibodies related to collagen diseases and tumour markers were all negative. Gallium scintigraphy showed abnormal accumulation in the left iliosacral joint, bilateral parotid glands, and acne lesions of the forehead (Fig. 2). CT scans of the pelvis showed increased space in the left iliosacral joint, thus suggesting swelling of the joint cartilage, but no solid-type periosteal reaction [6] were observed (Fig. 3). After admission, we treated the patient with intravenous antibiotics, but the clinical symptoms remained unchanged. For differential diagnosis, we performed a skin biopsy and found pyoderma with focal foreign body reaction and aberrant lymphoid cell infiltration (Fig. 4). We then started to administer oral ibuprofen. Clinical symptoms and laboratory findings improved rapidly after ibuprofen administration. Two years after discharge, his course has been uneventful with continued oral administration of ibuprofen. Because our case has not been refractory, we did not use pamidronate [4].

Les complications ostéoarticulaires des déficits immunitaires primitifs

Primary immune deficiencies (PIDs) are characterized by functional and/or quantitative abnormalities of one or more immune system components. Several bone and joint abnormalities can occur in patients with PID, with arthritis being the most common. • Joint manifestations, of which arthritis is the most common, occur chiefly in humoral PIDs (agammaglobulinemia, common variable immunodeficiency, hyper-IgM syndromes, and IgA deficiency) and occasionally in other PIDs (chronic granulomatous disease and Wiskott-Aldrich syndrome). Monoarthritis or oligoarthritis is the usual pattern, although polyarthritis may occur, occasionally with nodules suggesting rheumatoid arthritis. Arthritis in patients with PID is usually infectious in nature, the most common causative organism being Mycoplasma, followed by Staphylococcus, Streptococcus, and Haemophilus. These bacteria can induce not only synovial infections, but also aseptic arthritogenic inflammatory responses. Arthritis having no demonstrable relation to chronic infection has been reported also and ascribed to dysimmunity-driven mechanisms that exhibit a number of specific features. • Bone lesions are far less common and usually due to infections complicating humoral PID. Distinctive bone manifestations occur in a number of rare PIDs (e.g., hyper-IgE syndrome and Di-George syndrome) and in syndromes characterized by spondyloepiphyseal dysplasia. Familiarity with PID syndromes both enhances the diagnostic capabilities of physicians and provides insight into the pathophysiology of bone and joint abnormalities associated with immune dysfunction. • In children and occasionally in adults, a combination of bone and/or joint manifestations and hypogammaglobulinemia may indicate PID. When there is no evidence of lymphoproliferative disease, infection, or iatrogenic complications, investigations for PID should be obtained. • PID-related arthritis is a unique model for studying the pathogenesis of presumably postinfectious arthritis and of inflammatory joint diseases including rheumatoid arthritis.

Bone and joint disease associated with primary immune deficiencies

Primary immune deficiencies (PIDs) are characterized by functional and/or quantitative abnormalities of one or more immune system components. Several bone and joint abnormalities can occur in patients with PID, with arthritis being the most common. Joint manifestations, of which arthritis is the most common, occur chiefly in humoral PIDs (agammaglobulinemia, common variable immunodeficiency, hyper-IgM syndromes, and IgA deficiency) and occasionally in other PIDs (chronic granulomatous disease and Wiskott-Aldrich syndrome). Monoarthritis or oligoarthritis is the usual pattern, although polyarthritis may occur, occasionally with nodules suggesting rheumatoid arthritis. Arthritis in patients with PID is usually infectious in nature, the most common causative organism being Mycoplasma, followed by Staphylococcus, Streptococcus, and Haemophilus. These bacteria can induce not only synovial infections, but also aseptic arthritogenic inflammatory responses. Arthritis having no demonstrable relation to chronic infection has been reported also and ascribed to dysimmunity-driven mechanisms that exhibit a number of specific features. Bone lesions are far less common and usually due to infections complicating humoral PID. Distinctive bone manifestations occur in a number of rare PIDs (e.g., hyper-IgE syndrome and Di George syndrome) and in syndromes characterized by spondyloepiphyseal dysplasia. Familiarity with PID syndromes both enhances the diagnostic capabilities of physicians and provides insight into the pathophysiology of bone and joint abnormalities associated with immune dysfunction. In children and occasionally in adults, a combination of bone and/or joint manifestations and hypogammaglobulinemia may indicate PID. When there is no evidence of lymphoproliferative disease, infection, or iatrogenic complications, investigations for PID should be obtained. PID-related arthritis is a unique model for studying the pathogenesis of presumably postinfectious arthritis and of inflammatory joint diseases including rheumatoid arthritis.

Immune dysfunction in Camurati-Engelmann disease

Rationale Camurati-Engelmann disease (CED) is a progressive, autosomal dominant sclerosing bone dysplasia involving gene mutation of the latency-associated peptide of tumor growth factor (TGF)-β1, preventing inactivation of the cytokine. Since TGF-β is thought to play a regulatory role in immunity, one might expect an immune dysfunction in CED. Methods By retrospective chart review, a mother and daughter with CED were identified. Results The mother had a history of asthma, chronic gastrointestinal complaints, tobacco use, recurrent conjunctivitis, urinary tract infections, vaginal yeast infections, and monthly bronchitis. She had normal IgG and IgA, low IgG2, normal IgG4, low IgM of 48 (normal 60-263 mg/dl), and high IgE of 1709 (normal 2-120 IU/ml). However, she had inadequate anti-polysaccharide antibody response, anergy by DTH skin testing, and no response to recall antigens in vitro. She had normal serum TGF-β, but elevated serum IFN-γ, IL-4, and TNF-α. The daughter had documented CED gene mutation, bone pain, fatigue, loss of appetite, recurrent bronchitis and pharyngitis, requiring multiple courses of antibiotics. She had normal IgG and IgA, normal IgG subclasses, low IgM of 55, increased IgE of 192, normal anti-polysaccharide antibody response, and normal in vitro lymphocyte testing, but anergic DTH skin testing. Unlike her mother, she had non-detectable serum cytokine levels. Conclusions These patients reflect that gene mutation of the TGF-β1 latency-associated peptide is associated with immune dysfunction. Individual differences in immune abnormalities may parallel the variable, and progressive, bone manifestations seen in these patients. We anticipate the daughter's immune dysfunction to become more overt with age.

Is primary chronic osteomyelitis a uniform disease? Proposal of a classification based on a retrospective analysis of patients treated in the past 30 years

Introduction: Primary chronic osteomyelitis of the jaw is a rare, non-suppurative, chronic inflammatory disease of unknown aetiology. To date, classification is confusing due to a non-uniform terminology. The aim of this study was to establish a simple (clinical) classification based on patient data from our clinic. Methods: Retrospective analysis revealed 30 cases of which clinical course, radiology, pathology, therapy and outcome were analysed. Results: Both sexes were equally represented. The mean age at onset of disease was 35 years (range 5–76 years). Onset of disease revealed two peaks of incidence, one in adolescence and one after age 50 years. While clinical symptoms were similar in all cases, an increased intensity of these symptoms was noted in younger individuals as well as in the early stages of the disease. Five adults and one adolescent presented with additional non facial bone, joint and skin manifestations consistent with the diagnosis of SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome, or chronic recurrent multifocal osteomyelitis. Radiology demonstrated sclerosis, osteolysis and periosteal reaction in variable stages in all cases. However, findings were more extensive in younger patients. Histology revealed different stages of chronic inflammation in all cases. Microabscess formation was noted in 11 cases, six of which were children/adolescents. Therapy consisted mainly of surgery, antibiotics and hyperbaric oxygen therapy. At the end of the follow up period, 11 patients demonstrated complete remission, while in 14 cases amelioration and in 5 no significant improvement was noted. Conclusion: Based on differences in age at presentation, clinical appearance and course, radiology and histology, a subclassification into early and adult onset primary chronic osteomyelitis has been established. Cases with purely mandibular involvement should further be distinguished from cases associated with other syndromes.

Oncogenic Hypophosphatemic Osteomalacia Associated With a Nasal Hemangiopericytoma

We report a patient with a nasal hemangiopericytoma associated with an oncogenic hypophosphatemic osteomalacia (OHO). This syndrome results from tumor products that decrease renal tubular phosphate resorption, leading to the osteomalacia. This patient presented with classic bone manifestations of osteomalacia and a nasal tumor. Laboratory studies performed before the first resection of the tumor included normal serum calcium, hypophosphatemia due to decreased tubular reabsorption of phosphate, and an undetectable serum 1,25 dihydroxy vitamin D level. Serum parathormone level was normal. Anterior iliac crest bone biopsy showed characteristic signs of osteomalacia that included increased osteoid and delayed mineralization. A partial resection of the nasal tumor was performed. After the first surgery the patient showed detectable serum level of 1,25 dihydroxy vitamin D, and transient normalization of the tubular reabsorption of phosphate. The patient was also treated with phosphate supplements and vitamin D with transient control of her clinical manifestations and improvement of the radiographic signs of osteomalacia. Three months after surgery, the serum level of 1,25 dihydroxy vitamin D level again became undetectable. After selective embolization of the tumor, followed by an apparent complete tumor resection and postoperative radiation therapy, her hypophosphatemia and decreased phosphate tubular reabsorption persisted. Therefore, biochemical changes associated with hemangiopericytoma induced OHO may persist even after apparent total tumor resection. Clinicians should be aware of the oncogenic basis for some osteomalacia, as seen in this patient.

Les manifestations rhumatologiques de la mucoviscidose

Although bone and joint manifestations are common in children with cystic fibrosis, they have received little attention in adults. As compared to healthy individuals, bone mineral density is low, even with calcium intakes greater than 1500 mg/d. Nevertheless, calcium and phosphate levels in blood and urine are often normal, and vitamin D levels vary. Short stature with a low body mass index and central hy-pogonadism are the rule in these patients. Fractures and kyphosis are often reported. Cystic fibrosis arthropathy occurs in 2 to 8,5% of patients. Arthritis develops, and there may be skin eruptions. Nonsteroidal anti-inflammatory drug therapy is effective. Hypertrophic osteo-arthropathy associated with respiratory failure is present in 2 to 7% of patients. Rheumatoid arthritis, spondylo-arthropathies, sarcoido-sis, and amyloidosis have been reported in association with cystic fibrosis. Knee pain due to patellofemoral syndrome, quinolone-induced arthropathy, and mechanical back pain have been described. Rheumatoid factor titers are higher than in healthy controls, particularly in patients with episodic arthritis. No data are available on anti-perinuclear factor or antikeratin antibody titers. Tests for antinuclear antibody are usually negative. Circulating immune complex levels and antibodies to heat shock proteins may be elevated. Antineutrophil cytoplasmic antibody of the BPI or AZ type has been reported, often in high titers (up to 40%).

Musculoskeletal manifestations in cystic fibrosis

Although bone and joint manifestations are common in children with cystic fibrosis (CF), they have received little attention in adults. As compared to healthy individuals, bone mineral density is low, even with calcium intakes greater than 1500 mg/d. Nevertheless, calcium and phosphate levels in blood and urine are often normal, and vitamin D levels vary. Short stature with a low body mass index and central hypogonadism are the rule in these patients. Fractures and kyphosis are often reported. CF arthropathy occurs in 2–8.5% of patients. Arthritis develops, and there may be skin eruptions. Non-steroidal antiinflammatory drug therapy is effective. Hypertrophic osteoarthropathy associated with respiratory failure is present in 2–7% of patients. Rheumatoid arthritis, spondyloarthropathies, sarcoidosis, and amyloidosis have been reported in association with CF. Knee pain due to patellofemoral syndrome, quinolone-induced arthropathy, and mechanical back pain have been described. Rheumatoid factor titers are higher than in healthy controls, particularly in patients with episodic arthritis. No data are available on antiperinuclear factor or antikeratin antibody titers. Tests for antinuclear antibody are usually negative. Circulating immune complex levels and antibodies to heat shock proteins may be elevated. Antineutrophil cytoplasmic antibody of the bactericidal/permeability-increasing protein (BPI) or azurocidin (AZ) type has been reported, often in high titers (up to 40%).