Bone Manifestations Research Articles

Symptomatic and Scintigraphic Improvement after Intravenous Pamidronate Treatment of Paget’s Disease of Bone in Patients with Normal Serum Alkaline Phosphatase Levels

To describe three patients with symptomatic Paget's disease of bone who presented with normal levels of serum alkaline phosphatase. We present three cases of Paget's disease of bone and chronicle the laboratory, scintigraphic, and clinical findings relative to treatment with intravenously administered pamidronate. Although measurement of serum total alkaline phosphatase usually provides a general indication of bone turnover in Paget's disease, about 15% of patients present with normal serum alkaline phosphatase levels. Nonetheless, these patients may have active Paget's disease when assessed with bone scintigraphy or urinary markers of bone resorption. All three study patients had xray findings characteristic of Paget's disease of bone, increased uptake of radiotracer material on bone scans, and elevated levels of urinary markers of bone resorption but normal alkaline phosphatase levels. They were treated with intravenously administered pamidronate, 60 mg once weekly for 2 to 3 consecutive weeks. After treatment, the serum alkaline phosphatase level decreased by 19 to 36%, markers of bone resorption normalized, bone scans showed improvement, and bone pain resolved. Pagetic activity in bone and related clinical manifestations may be present in the setting of a normal serum alkaline phosphatase level. Appropriate therapy should not be withheld because of the normal alkaline phosphatase.

A new approach to treat tissue destruction in periodontitis with chemically modified dextran polymers.

Periodontitis are diseases of the supportive tissues of the teeth provoked by bacteria and characterized by gingival inflammation and bone destruction. We have developed a new strategy to repair tissues by administrating agents (RGTA) that mimic heparan sulfates by protecting selectively some of the growth factors naturally present within the injured tissue and interfering with inflammation. After periodontitis induction in hamsters, the animals were left untreated or received weekly i.m. injections of RGTA1507 at a dose of 100 microg/kg, 400 microg/kg, 1.5 mg/kg, or 15 mg/kg for 4 wk. RGTA treatment significantly reduced gingival tissue inflammation, thickened the pocket epithelium by increasing cell proliferation, and enhanced collagen accumulation in the gingiva. A marked reduction in bone loss was observed, resulting from depression of osteoclasia and robust stimulation of bone formation at the dose of 1.5 mg/kg. RGTA treatment for 8 wk at this dose reversed macroscopic bone loss, sharply contrasting with the extensive bone destruction in the untreated animals. RGTA treatment decreased gelatinase A (MMP-2) and B (MMP-9) pro-forms in gingival tissues. Our data indicate that a 4 wk treatment dose-dependently attenuated gingival and bone manifestations of the disease, whereas a longer treatment restored alveolar bone close to controls. By modulating and coordinating host responses, RGTA has unique therapeutic properties and is a promising candidate for the treatment of human periodontitis.

A Study of Musculoskeletal Manifestations in 12 Patients with SAPHO Syndrome

Synovium and synovial fluid findings in SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome have not been well characterized, and only a few patients have been described in the Americas. We describe clinical, pathologic, and synovial fluid findings in 12 patients with the SAPHO syndrome: hidradenitis suppurativa (7), acne fulminans or conglobata (3), acneiform folliculitis (1) and palmoplantar pustulosis (1). Routine synovial fluid studies were performed in 6 patients, and light and transmission electron microscopic studies were performed in synovium in 2 patients and in bone in 1. The most common musculoskeletal manifestations included erosive or non-erosive oligoarthritis involving metacarpal phalangeal (MCP) and metatarsal phalangeal (MTP) joints as seen in 9 patients, sclerosis of the sacroiliac joints as seen in 5 patients, and osteitis pubis as seen in 1. Three patients had signs of skeletal hyperostosis. The patients with acne fulminans and acneiform folliculitis had chronic aseptic multifocal osteomyelitis. Synovial fluid was sterile in 7, mildly inflammatory in 5, and highly inflammatory in 2. Electron microscopic studies of synovium in 2 patients and of bone in 1 were not useful to detect microorganisms. Three African-American patients with hidradenitis suppurativa presented with pyoderma gangrenosum, and 2 of them had leukocytoclastic vasculitis, and a life threatening course unresponsive to antibiotics, corticosteroids and immunosuppressive therapy. SAPHO in the Americas is most severe in African-Americans with hidradenitis suppurativa, and it presents with heterogeneous musculoskeletal and cutaneous manifestations including erosive polyarthritis or oligoarthritis with nonspecific mild inflammatory fluid. Leukocytoclastic vasculitis and recalcitrant pyoderma gangrenosum were seen in 2 of our patients with the most severe hidradenitis suppurativa. SAPHO syndrome may present with clinical manifestations similar to those seen with seronegative spondyloarthropathies, but it has distinctive cutaneous, radiographic articular, and bone manifestations. Sites of chronic infection need aggressive antibiotic therapy and may need surgical resection.

La Maladie de Gaucher

Gaucher disease is an uncommon autosomic recessive disorder. The disease is caused by a deficiency in the activity of the lysosomal enzyme glucocerebrosidase which is responsible for the degradation of glucosylceramide, résulting from the breakdown of red and white cell-membranes. In the absence of enzyme glucosylceramide accumulates in the lysosomes of macrophages. This accumulation leads to hepatomegaly, splenomegaly with subsequent haematologic abnormalities (leucopenia, anemia, thrombopenia) and bone manifestations. Three types of Gaucher disease are described: type 1 is the most common, type 2 and 3 are associated with neurologic symptoms. Macrophages are the likely cellular source of biochemical abnormalities: elevated blood level of ferritin, angiotensin converting enzyme, immunoglobulins and haemostasis abnormalities. Lysosomal perturbations lead to increased blood level of tartrate resistant acid phosphatase and chitotriosidase. Enzyme replacement therapy is available in France since 1991. In 2002, 136 patients are treated. The efficacy is overt on the asthenia, organomegaly and haematological manifestations. Bone pains disappear or decrease in intensity, however bone complications may be irreversible justifying treatment initiations before the appearance of lesions that may lead to serious functional impairment.

Lung Transplantation for Cystic Lung Diseases: Lymphangioleiomyomatosis, Histiocytosis X, and Sarcoidosis

Lung transplantation for respiratory failure due to lymphangioleiomyomatosis, histiocytosis X, and sarcoidosis is a therapeutic option in selected patients. These indications account for less than 6% of all lung transplant procedures, and experience is relatively scarce. Pulmonary function testing at evaluation usually shows an obstructive pattern in lymphangioleiomyomatosis, whereas histiocytosis presents with a mixed pattern, and sarcoidosis with a restrictive pattern. Lung diffusion capacity is similarly reduced, however, only histiocytosis and sarcoidosis are often associated with pulmonary hypertension. In all three diseases extrapulmonary manifestations, although of different kinds, are common and must be investigated before transplantation to avoid posttransplant diagnostic pitfalls. In all these diseases, single and bilateral transplantation show comparable results. Typical complications in lymphangioleiomyomatosis include intraoperative severe intrathoracic bleeding, posttransplant chylothorax, pneumothorax, and bleeding of angiomyolipomas. In histiocytosis, extrapulmonary manifestations in bones and pituitary gland may progress. These diseases typically recur in the allograft, leading to clinical symptoms in histiocytosis whereas recurrence in lymphangioleiomyomatosis and sarcoidosis is most often asymptomatic. Survival is similar to patients transplanted for other diseases.

Les manifestations osseuses de l'alitement prolongé

Introduction: Bone manifestations of long lasting bed rest may be responsible of increased risk fracture. These manifestations remain unknown before mechanical complications. They consist in increased bone resorption and negative calcium balance conducting to accelerated bone loss. Accelerated bone loss appears after 5 - week bed rest. Method – Results: It has been described by densitometry to reach –3,6% at the femoral neck, –3,9% at the lumbar spine, and –10,4% at the calcaneum, after 4 months. Its reversibility appears unclear but few data concerning this process are now available. Discussion – Conclusion: Physicians should be aware of accelerated bone loss and develop early strategies for prevention in patients at risk of long lasting bed rest. Physical therapy including repetitive contractions of pelvitrochanteric muscles in several sessions daily is proposed for this purpose. Indeed, similar trainings have been reported to prevent bone loss in other situations, characterized as well as long lasting bed rest, by accelerated bone loss and consequent increased risk fracture.

Diffuse Swelling of One Finger in a Patient with Metastatic Breast Cancer

Tumor metastases distal to the elbow, and specifically in the hand, are extremely rare. The diagnosis can be difficult, because these lesions can resemble those of rheumatoid arthritis, other inflammatory arthritis, and osteomyelitis. Therefore, rheumatologists should consider metastasis to the limbs in the differential diagnosis of individuals who present with joint or bone manifestations and history of cancer, even if remote. We report a woman with breast cancer and metastatic disease predominantly affecting one finger.

A Hospital-Based Survey of Primary Hyperparathyroidism in the Asir Region: Low Prevalence or Underdiagnosis?

The number of patients with primary hyperparathyroidism (PHP) seen at the Asir Central Hospital (ACH) is remarkably low. This observation has raised the question of whether there is a low prevalence of PHP in the Asir region, whether it is underdiagnosed, or perhaps a combination of both factors. A survey of 15 hospitals in the Asir region was conducted for cases of PHP. All case notes of the patients with PHP seen at ACH were reviewed. Also, a sample of patients seen at ACH was chosen randomly. The charts of those found to have hypercalcemia were reviewed for the inclusion of PHP in the diagnostic work-up. Only 13 patients with PHP were discovered. The eight patients with PHP seen at ACH had advanced bone manifestations and seven of them had renal manifestations. Hypercalcemia was found in 39 out of 655 patients seen at ACH. None of these had been investigated for PHP. The number of patients with PHP seen in hospitals in the Asir region is very low. Underdiagnosis seems to be an important factor. Therefore, it is felt that there is a need for greater awareness of the disease in the region. Furthermore, there is a need for a national survey to measure the prevalence of PHP in Saudi Arabia.

Oropharyngeal leprosy in art, history, and medicine

Advanced lesions of the face, nasopharynx, and oropharynx have played an important role in the medical and social history of Hansen’s disease. Renaissance artists included detailed portrayals of these lesions in some of their paintings, a testimony not only to their artistic skill and powers of observation but also to the common presence of these patients in European cities and towns of the period. The disease is now understood as a broad immunologic spectrum of host responses to Mycobacterium leprae , with a variety of clinical and pathologic manifestations in nerve, soft tissues, and bone. This review incorporates the findings of 2 extraordinary studies (one from Europe and the other from Japan) of pharyngeal and facial lesions. In the 1950s, studies of skeletal remains from the churchyard of a Danish leprosarium revealed a triad of maxillofacial lesions unique to leprosy and designated facies leprosa . In pre–World War II Japan, before effective treatment had been discovered, a prominent otorhinolaryngologist studying oropharyngeal and nasopharyngeal lesions prepared watercolor illustrations of the natural progression of untreated Hansen’s disease. As a result of effective antimicrobial therapy, such advanced lesions are now rarely seen, but the presenting signs and symptoms of leprosy still occasionally arise in the nasal and oral mucosa. The nasopharynx and oropharynx may be important early sites of inoculation and infection by M leprae , and they require additional emphasis in worldwide efforts toward early diagnosis and treatment of Hansen’s disease. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:463-70)

Rheumatoid Arthritis: Evaluation of Temporomandibular Joint Abnormalities with MR Imaging

It is well known that the temporomandibular joint (TMJ), as well as other joints, may be affected in patients with rheumatoid arthritis (RA). Conventional radiographic methods can be used in the assessment of bone damage but its usefulness is limited as the soft tissue involvement cannot be demonstrated. Many reports have shown the potential of magnetic resonance imaging in the evaluation of different TMJ components, all of which are often compromised in rheumatic disease; moreover MR imaging is superior for depicting advanced stages of rheumatic disease with various degrees of disc destruction. The purpose of this study was to evaluate the role of MR imaging in the assessment of RA. MR imaging of the TMJ was performed on 14 patients (11 women and 3 men, aged 36–79 years, mean 57.5) with diagnosed RA in stages 2 and 3 according to Steinbroker criteria. Both TMJs were evaluated in ten patients. A total of 24 TMJs were studied in this group of patients. Informed consent was obtained in each case. The goal of MR is not only to facilitate a diagnosis of rheumatoid arthritis, which may be done using laboratory and clinical parameters, but to assess the extent of the early soft-tissue and bone manifestations of the inflammatory process and to identify the stage of the disease.

Bone and soft tissue manifestations of alveolar echinococcosis

The present study demonstrates the osseous and soft tissue manifestations of alveolar echinococcosis (AE). We report on eight patients with AE with bone or soft tissue involvement confirmed at biopsy or needle cytology. All eight patients showed hepatic involvement. Four exhibited infiltration of the spine as a result of direct spread of the hepatic primary lesion; distant metastases were observed in only three of these patients. Calcifications, which are typical for hepatic manifestations of the disease, were observed in soft tissue in only two of eight cases (25%); we observed no instances of endovesicular daughter cysts. AE manifests itself in the vertebral column as a form of spondylitis and in soft tissue presents similar to an abscess. Since in most of these cases spread of the disease per continuitatem from the liver is present, the diagnosis is easily made from the characteristic hepatic findings.

Die chronisch rekurrierende multifokale Osteomyelitis (CRMO). Kurze Literaturübersicht, Nosologie, diagnostische Kriterien und rheumatologische Differentialdiagnose*

The rare disease of "chronic recurrent multifocal osteomyelitis" (CRMO) is reviewed from the world literature. CRMO is an acquired, aseptic skeletal disease mostly affecting children and young adolescents. The adult manifestation of CMRO often becomes a rheumatological problem of differential diagnosis: "Adult CRMO". This disease is based on a smoldering lymphoplasmacellular and chronic osteomyelitis which is most likely associated with immunopathogenetic mechanisms and consecutively self limiting sclerosis. This immunopathogenetic process may be triggered by infections. In 25% of the cases an association with the bone and cutaneous manifestations of pustulosis palmo-plantaris has been reported which has been suggested to be of psoriatic origin. Clinical, radiographic and histopathological data are referred from the literature. We suggest diagnostic criteria and discuss the broad differential diagnosis of this disease entity within the hyperostotic spondarthritides. The difficulties in attempts to classify CRMO as SAPHO syndrome are emphasized. The hypothesis of the immunopathogenesis of "chronic poly-osteomyelitis" is outlined and aims of further investigations on CRMO are defined.

Interrelationships of food, nutrition, diet and health: the National Association of State Universities and Land Grant Colleges White Paper.

Nutrition and food science have each enhanced the development of an abundant, nutritious, safe food supply. A healthy diet should contain all of the required nutrients and sufficient calories to balance energy expenditure and provide for growth and maintenance throughout the life cycle. Importantly, dietary factors are associated with 5 of the 10 leading causes of death, including coronary heart disease, certain types of cancer, stroke, noninsulin dependent diabetes mellitus and atherosclerosis. National health care expenditures for 1990 totaled $666 billion of which 30% are related to inappropriate diet. Identification of external factors that contribute to premature death would aid preventive efforts, improve the quality of life, and reduce health care costs. Even though genetic predisposition increases susceptible people's risk for many of these chronic diseases, these conditions may be diminished or prevented by improvements in the American diet. Each stage of the life cycle has specific nutrient needs. Throughout infancy, childhood and adolescence nutrients are required to meet the growth processes as well as cognitive function. During pregnancy nutrients are required for both mother and developing infant needs. Adult nutrition focuses on tissue maintenance, nutrient and energy needs, and disease prevention. As the population of elderly increase in number and greater age, nutritional needs must be met to minimize certain disease states and assure the quality of life. Nutrition associated health risks have been identified for coronary heart disease, cancer and diabetes mellitus. Recommendations for each includes a decrease in dietary fat, awareness of caloric intake and enhancement of nutrient density including an increase in fruit and vegetables. These recommendations also impact obesity and diminish the compounding of other disease states affected by excessive body weight. Calcium intake at early ages affects development of bone density and manifestation of osteoporosis. Current gaps in knowledge are also identified that could improve health. Numerous nutrients are being examined for their regulation of specific gene expressions and in the processes of transcription and translation. To offer food products with greater nutrient density or improved functional health ingredients, modification of existing foods is needed to assure an improved diet. Policies to improve health require integration of nutrition needs with economic growth and development, agriculture and food production, processing, marketing, health care and education, and includes changing life styles and food choices. Increased research support is required to achieve national health goals with emphasis on nutrition and food sciences. Education methods must be improved to better inform consumers, to encourage food producers and manufactures to produce healthier foods, to assure training of future professionals and to provide legislators with the basis to make informed decisions. Recommendations to CFERR are identified. Improved quality and availability of nutritious foods will result in a healthier, more productive population. A decrease in the occurrence and duration of chronic disease should diminish the cost of health care and allow these resources to further benefit the nation. International concerns about undernutrition include 780 million people who are malnourished, lacking sufficient food to meet their basic nutritional needs for protein and energy, and 2 billion people who subsist on diets lacking essential nutrients needed for growth, development and physiological maintenance. National concerns about undernutrition exist based on incomplete data identified by indices of hunger and characterized by an increased demand for food assistance for women, children and the elderly. Major health problems in the US impacted by diet and nutrition include coronary heart disease, atherosclerosis, some types of cancer, non-insulin dependent diabetes mellitus, hypert

Evidence for McKusick's hypothesis of deficient collagen cross-linking in patients with homocystinuria

Osteoporosis occurs commonly in homocystinuria. The underlying pathobiochemical mechanism remains unclear: disturbed cross-linking of collagen has been suggested but this hypothesis has not been fully tested, nor have studies on collagen synthesis been performed. We therefore used recently available noninvasive tests for collagen synthesis and cross-linking to examine 10 patients with homocystinuria. Synthesis of collagen type I and type III was not different from age-matched healthy controls as reflected by comparable plasma levels of carboxyterminal propeptide of type I procollagen (PICP) and of plasma levels of N-terminal propeptide of procollagen type III (PIIINP). Collagen type I cross-links expressed by serum carboxyterminal telopeptide of collagen type I (ICTP) were 1.14 ± 0.24 μg/l in the patient group versus 3.29 ± 0.32 μg/l in the control group. This significant reduction of cross-links in the group with homocystinuria did not correlate with serum homocysteine or homocysteic acid concentrations. Our data clearly indicate that the disturbed cross-linking hypothesis still holds and that the bone manifestations of homocystinuria are not due to deficient collagen synthesis.

Assessing deficiency and excessive iron in children

Mastocytosis is a heterogeneous group of clonal mast cell disorders in which bone manifestations are frequently seen, but poorly understood. In this study, we analyzed correlation of clinical findings in mastocytosis patients with bone mineral density and bone turnover markers.Serum levels of bone turnover markers were measured in mastocytosis patients and healthy volunteers. Bone disease was evaluated using radiographic imaging, and measurement of bone mineral density.Of 45 adult mastocytosis patients, bone abnormalities were detected in 34 (75%). Bone lesions were documented on radiographic imaging in 16 patients (36%), and bone mineral density in 24 patients (53%), of which 9 patients (20%) had osteoporosis and 15 (33%) had osteopenia. Serum levels of bone turnover markers that evaluate bone resorption (C-telopeptide, deoxypyridinoline), bone formation (bone-specific alkaline phosphatase), and bone remodeling (osteoprotegerin) were significantly higher in the patient population than in the control population (n = 28). Levels of C-telopeptide and osteoprotegerin were higher in patients with advanced systemic mastocytosis than in patients with cutaneous or indolent systemic mastocytosis. Moreover, C-telopeptide and osteoprotegerin levels were significantly correlated with those of serum tryptase, a diagnostic marker of mastocytosis.The observed bone turnover markers variations indicate a complex process of bone turnover in mastocytosis-related bone manifestations. The highly significant correlation between serum tryptase and serum bone turnover markers levels, and the positive correlation of levels of bone turnover markers with advanced disease, support the existence of a link between bone remodeling and mast cell burden.

Bone and joint manifestations of hypothyroidism

Hypothyroidism is frequently accompanied by musculoskeletal manifestationsranging from myalgias and arthralgias to true myopathy and arthritis. A case is presented in which an arthropathic process in the hip was the isolated finding in a young man who was severely hypothyroid. Previous literature on bone and joint manifestations of hypothyroidism is reviewed, with emphasis on cases where such manifestations were the presenting symptoms of thyroid dysfunction. Most cases of arthropathic changes in adult-recognized hypothyroidism involved the knees and hands, while the hip and the epiphysis of the femoral head appear more commonly involved in children. Thyroid hormones have known effects at the cellular level on proliferation and differentiation of bone and cartilage. The hypothyroid state appears to induce abnormalities in these tissues, which result in such clinical manifestations as epiphyseal dysgenesis, aseptic necrosis, possibly crystal-induced arthritis, and an arthropathy characterized by highly viscous noninflammatory joint effusions primarily affecting the knees, wrists, and hands. Neuropathic and myopathic symptoms accompanying hypothyroidism may manifest as joint region abnormalities when in fact there is no underlying arthropathy.

Syndrome primaire des antiphospholipides d'évolution fatale et cytostéatonécrose ostéoarticulaire

A 58 year-old-man had fat necrosis and joint and bone manifestations associated with antiphospholipid antibody. After pulse steroid therapy, he developed a fatal devastating syndrome with multiple, non-inflammatory occlusions of large and small vessels.

Can Vitamin D Deficiency Produce an Unusual Pain Syndrome?

To the Editor.— Gloth et al 1 presented five patients with unusual leg pain in the presence of abnormal serum vitamin D levels, which resolved rapidly after vitamin D supplementation. Several of these patients had diffuse demineralization and risk factors for developing osteomalacia, but no systematic efforts to document characteristic Looser zones in the pelvis or shoulder girdle were reported. Also, results of leg roentgenograms that could have shown localized bone demineralization were not reported. Peripheral bone manifestations with excruciating bone pain and features of causalgia, algodystrophy, regional painful osteoporosis, or reflex sympathetic dystrophy as a result of osteomalacia have been described previously in both the American and the European literature. 2,3 We have seen this syndrome both in sporadic cases of osteomalacia and in the elderly in whom the syndrome is misdiagnosed as part of generalized senile osteoporosis as well as in younger patients living in the Chilean Patagonia

Radiographic interpretation in orofacial disease : Porter SR, Scully C (eds), with six contributors. New York, NY, Oxford University Press, 1991, 109 pages, illustrated, paperback, $37.50

In a question and answer format, this textbook shows students how to interpret various types of radiographs: intra-oral periapical bitewing and skull views, CAT scans and sialograms. It covers common dental, oral and maxillary disorders as well as anatomical anomalies and dental, bone and joint manifestations of sytemic disease. The book is an attempt to prepare students for clinical practice and examinations. It is not however intended to be comprehensive and should be used in conjunction with standard texts on the subject.

Luteinizing Hormone-Releasing Hormone (LHRH)-Independent Precocious Puberty Unresponsive to LHRH Agonist Therapy in Two Girls Lacking Features of the McCune-Albright Syndrome

Two girls with precocious puberty (chronological age, 1 and 4 yr; bone age, 3 and 6 yr, respectively) were initially given the diagnosis of idiopathic, central precocious puberty and treated with the LHRH agonist deslorelin (D-Trp6-Pro9-NEt-LHRH) for 5 yr. Unlike other girls with central precocious puberty, both had persistently elevated rates of growth and bone maturation, and both menstruated during therapy. One girl had episodic ovarian enlargement and markedly elevated serum estradiol levels due to recurrent unilateral ovarian cysts. Although the bone and skin manifestations of McCune-Albright syndrome were absent, we hypothesize that the underlying defect of McCune-Albright syndrome was expressed in the ovaries, but not in the skin or bones, of these two girls. One of these girls appeared to benefit from the aromatase inhibitor testolactone, which is effective in suppressing precocious puberty in girls with the McCune-Albright syndrome.