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Biomedical subjects

C Marcelli

Publications and source records attributed to C Marcelli.

At least 37 records · Page 2Linked to original sources

Markers of bone resorption predict hip fracture in elderly women: the EPIDOS Prospective Study.

Increased bone turnover has been suggested as a potential risk factor for osteoporotic fractures. We investigated this hypothesis in a prospective cohort study performed on 7598 healthy women more than 75 years of age. One hundred and twenty-six women (mean years 82.5) who sustained a hip fracture during a mean 22-month follow-up were age-matched with three controls who did not fracture. Baseline samples were collected prior to fracture for the measurement of two markers of bone formation and three urinary markers of bone resorption: type I collagen cross-linked N- (NTX) or C-telopeptide (CTX) and free deoxypyridinoline (free D-Pyr). Elderly women had increased bone formation and resorption compared with healthy premenopausal women. Urinary excretion of CTX and free D-Pyr, but not other markers, was higher in patients with hip fracture than in age-matched controls (p = 0.02 and 0.005, respectively). CTX and free D-Pyr excretion above the upper limit of the premenopausal range was associated with an increased hip fracture risk with an odds ratio (95% confidence interval) of 2.2 (1.3-3.6) and 1.9 (1.1-3.2), respectively, while markers of formation were not. Increased bone resorption predicted hip fracture independently of bone mass, i.e., after adjustment for femoral neck bone mineral density (BMD) and independently of mobility status assessed by the gait speed. Women with both a femoral BMD value of 2.5 SD or more below the mean of young adults and either high CTX or high free D-Pyr levels were at greater risk of hip fracture, with an odds ratio of 4.8 and 4.1, respectively, than those with only low BMD or high bone resorption. Elderly women are characterized by increased bone turnover, and some markers of bone resorption predict the subsequent risk of hip fracture independently of hip BMD. Combining the measurement of BMD and bone resorption may be useful to improve the assessment of the risk of hip fracture in elderly women.

Absorptiometry, Photon↗

[Epidural lipomatosis: complication of long-term corticotherapy. Apropos of 2 cases].

Spinal epidural lipomatosis (SEL) is defined as the deposition of loose fat tissue in the epidural space. Two cases are reported which illustrate the main features of this uncommon disease. Most frequently SEL is revealed by neurologic manifestations such as an acute chronic spinal cord compression. Corticosteroid therapy and obesity are the main factors able to induce the disease. The common location of the SEL at the thoracic spine is explained by the physiologic abundance of fat and by the relative narrowness of the spinal canal at this level. An osteoporotic vertebral crush fracture which reduces the diameter of the canal frequently reveals the SEL. MRI confirms the diagnosis of SEL and shows the extent in the spinal canal. The treatment of SEL is difficult. The decrease or the stop of corticosteroid therapy has allowed the recovery in a few cases with chronic neurologic symptoms. The risks of a surgical procedure are important in these patients and the medical or surgical treatment should be discussed taking into account the clinical symptoms of SEL, its location and extent, and the risks of recurrence if corticosteroid therapy must go on.

Adult↗

[Secondary osteoporosis].

Although primary osteoporosis is much more frequent than other diseases associated with osteopenia, the diagnosis of idiopathic osteoporosis should be made only after the causes of secondary osteoporosis have been excluded. Indeed, therapeutic efficiency in secondary osteoporosis depends mainly on the concomitant treatment of the actual cause of osteopenia. Glucocorticoid-induced osteoporosis is the commonest form of secondary osteoporosis, mainly for doses of prednisone of 0.1 mg/kg/day or greater. Hypogonadism in men and women, idiopathic hypercalciuria and chronic alcoholism in men are other frequent causes of osteopenia. The diagnosis of secondary osteoporosis is based on careful examination as well as biochemical and hormonal investigations. Together with the treatment of the associated disease, correction of other risk factors, calcium supplementation, and a regular program of weight-bearing physical activity may be of benefit to reduce bone loss. As fluoride is able to stimulate bone formation, it is an effective agent in the treatment of glucocorticoid or alcohol-induced osteoporosis.

Adrenal Cortex Hormones↗

Pagetic vertebral ankylosis and diffuse idiopathic skeletal hyperostosis.

STUDY DESIGN: A retrospective radiologic analysis of Paget's disease of the spine. OBJECTIVES: The prevalence, anatomic distribution, mechanisms of formation of Pagetic vertebral ankylosis (PVA) and the possibility of a relationship to diffuse idiopathic skeletal hyperostosis (DISH) were assessed in a large population of persons with Paget's disease. SUMMARY OF BACKGROUND DATA: Acquired vertebral ankylosis is not a common feature of the Paget's disease of the spine and its mechanisms of formation remain unknown. In some reports, PVA was associated with radiographic signs of DISH. METHODS: Of 337 Pagetic patients monitored in the Division of Rheumatology from 1961 to 1990, all 245 who had entire spine radiographs were selected for study. Radiographs were studied for signs of Pagetic vertebral lesions and for spinal lesions of DISH. RESULTS: The study group contained 156 men with a mean age of 68 years (range 37-92) and 89 women with a mean age of 71 years (range 50-89). Fourteen PVA were observed on the radiographs of 11 men (mean age 68 years; range 60-76). One PVA was cervical, eight were thoracic, one thoracolumbar, three lumbar, and one lumbosacral. Eighty of the two hundred forty-five patients (32.6%) had characteristic features of DISH. Eight out of the eleven patients with PVA also had evidence of spinal lesions of DISH and radiographic features of DISH were observed contiguous to ten of the fourteen PVA. CONCLUSIONS: The scarcity of PVA reported in the literature and in our study (4.4% of 245 patients) suggests that constant progression of the disease from one vertebra to another by invasion of intervertebral disc space is rare. However, the higher incidence of PVA in men, their preferential location at the thoracic spine and their association with lesions of DISH suggest that progression of Pagetic lesions by invasion of bridging osteophytes may be an important mechanism for the intervertebral spread of Paget's disease.

Adult↗

The relationship between osteoarthritis of the hands, bone mineral density, and osteoporotic fractures in elderly women.

To study the relationship between osteoarthritis (OA) and osteoporosis (OP), radiographic osteoarthritis lesions of the hands (HOA) were quantified in 300 healthy women, aged 75 years or more, as a subgroup of a cohort originally recruited for a multi-centre study of risk factors for femoral neck fracture. The HOA combined score (i.e. the sum of the grades of joint-space narrowing, osteophytes, erosions and joint misalignment), the osteophytosis score and the joint-space narrowing score were calculated on a radiograph of both hands. Bone mineral density (BMD) was measured using dual-energy X-ray absortiometry (Lunar DPX) at the femoral neck, Ward's triangle and the total body. BMDs of the total spine, lumbar spine, and the upper and lower limbs were derived from the regional analyses of the total body measurement. Correlations between bone mass, HOA scores and other variables were explored by multiple linear regression and stepwise logistic regression analysis. The HOA combined score was positively correlated with increasing age but not with body mass index. In the multiple regression analyses the HOA combined score positively correlated with BMD and the joint-space narrowing score. According to stepwise logistic regression and after off adjustment of BMD for age, women with an HOA combined score higher than 20 had significantly higher BMD values at all skeletal sites. Sixty-nine women (23%) reported a history of osteoporotic fracture; among them, 20 (6.6%) reported a history of vertebral fracture. The OA score of both subgroups was significantly lower than that of women with no history of fracture. These data suggest that in elderly women the severity of HOA is positively correlated with bone mass and that women with a higher score of HOA more rarely report a history of osteoporotic fracture.

Aged↗

[Effects of an hydrosoluble fraction from bovine bone (Ossopan) on murine osteoblasts in culture].

The effects of an hydrosoluble fraction of the bovine bone extract Ossopan on cultured murine osteoblasts were assessed in this study. The hydrosoluble fraction from Ossopan, obtained by acid/ethanol extraction, contained significant amounts of TGF-beta 1. Calvariae from new-born rats were cultured for 1 month in synthetic medium (DMEM) supplemented with 10% fetal calf serum to allow cell proliferation; immunocytochemistry studies performed with a rabbit serum raised against alkaline phosphatase indicated that only osteoblasts were present in cell cultures. Using an XTT-based colorimetric cell proliferation assay, we showed that the hydrosoluble fraction of the bovine bone extract dose-dependently reduced the proliferation of cultured osteoblasts. A similar inhibition was obtained with a recombinant TGF-beta 1. Thus, the inhibitory effect of the hydrosoluble fraction of Ossopan on osteoblast proliferation should be due to the cytokines contained in this preparation.

Animals↗

[Fluoride therapy. Influence on the microarchitecture and biomechanical properties of bone].

Fluoride, in the form prescribed as sodium or monophosphate fluoride for the treatment of vertebral osteoporosis, modifies the microscopic structure and biomechanical properties of bone tissue. For cancellous bone, the main effect of fluoride is a stimulation of bone formation leading to a hypertrophy of the remaining trabeculae. It may also have a beneficial effect by improving interconnections within the trabecular network. Although the mechanisms have yet to be fully understood, the process is probably dependent on the quality of the remaining network. The biomechanical properties of bone after fluoride therapy also are partly dependent on these modifications in the bone microstructure but also on fluoride's effect on bone minerals. When the concentration of fluoride becomes too high in bone, mineralization defects can occur causing major loss in mechanical resistance despite an increase in bone mass. Thus the beneficial effect of fluoride on wedge fractures of the spine in osteoporosis is probably the result of a balance between the effects of increased trabecular bone mass and modifications in bone mineralization. The respective intensities of these two phenomena also depend on the concentration of fluoride accumulated within the bone. This concentration is a function of the level of fluoride salt intake and its biodisponibility during treatment.

Biomechanical Phenomena↗

Adult lumbar scoliosis. Epidemiologic aspects in a low-back pain population.

The frequency and characteristics of definite lumbar scoliosis in an adult common low-back pain population (n = 671) were assessed by a clinical and radiologic prospective study. The prevalence was 7.5% (N = 50), increasing with age: 2% before 45 years; 15% after 60 years. Scoliosis was revealed by low-back pain in adulthood in 86% of the cases. The mean Cobb angle was 21 +/- 11.4 degrees. A Cobb angle of more than 30 degrees was noted in 16% of the scoliotics, thus 1% of the entire population. The proportion of women increased with the severity of the scoliosis. Right and left side scolioses were equally noted. A correlation between the Cobb angle and age was found (0.3 degrees/yr; P < 0.05). Rotatory olisthesis was noted in 34% of the cases, more often in right side curves (P < 0.01). The lumbar scoliotic patients were distinguished by a more advanced age (62 +/- 12.4 yr vs. 49.6 +/- 15.5 yr; P < 0.001), a greater proportion of women (72% vs. 48%; P < 0.01), and a more likely involvement of L3 and L4 radicular pain (P < 0.05). Radicular thigh pain was related to unstable curves (P < 0.01). The lumbar scoliotic patients thus constitute a subgroup within the low-back pain population.

Adult↗

[Mechanisms of spinal block formation in Paget disease of bone. Radiographic study based on 14 cases].

Vertebral bridging occurs in approximately 10% of patients with spinal pagetic lesions. Diffuse idiopathic skeletal hyperostosis has been reported in patients with pagetic block vertebras and may facilitate vertebral fusion and extension of pagetic lesions. High prevalences of diffuse idiopathic skeletal hyperostosis have been found in patients with Paget's disease. To determine how pagetic block vertebras develop and to investigate relationships between Paget's disease and diffuse idiopathic skeletal hyperostosis, 244 patients with Paget's disease were studied retrospectively. Diagnostic criteria for diffuse idiopathic skeletal hyperostosis were the presence of flowing ossification along the anterolateral aspect of at least three contiguous vertebral bodies or presence of at least two anterolateral intervertebral bony bridges in the same spinal segment. Eight (33%) of the 244 patients had diffuse idiopathic skeletal hyperostosis. Two-thirds of patients with both conditions were male. There was no statistically significant association between presence of diffuse idiopathic skeletal hyperostosis and spinal involvement by Paget's disease. Fourteen pagetic block vertebras were identified in 11 male patients. Eight of these 11 patients had involvement of the fused vertebras or adjacent vertebras with diffuse idiopathic skeletal hyperostosis. Our findings confirm that diffuse idiopathic skeletal hyperostosis is common in patients with Paget's disease. The statistically significant association between diffuse idiopathic skeletal hyperostosis and pagetic vertebral fusion in the same site suggests that the former condition may be a risk factor for pagetic vertebral bridging.

Adult↗

Expression of human transforming growth factor alpha by Chinese hamster ovarian tumors in nude mice causes hypercalcemia and increased osteoclastic bone resorption.

Transforming growth factor alpha (TGF-alpha) is a polypeptide regulator of cell growth produced by many malignant tumors. It stimulates osteoclastic resorption in bone organ culture and osteoclast-like cell formation in marrow culture. To determine whether tumor production of TGF-alpha can cause hypercalcemia in vivo, we used Chinese hamster ovarian (CHO) cells transfected with the human TGF-alpha gene (TCHO), which stably express and secrete TGF-alpha. We used nontransfected CHO cells as controls (CCHO). TCHO and CCHO were inoculated intramuscularly into one hindlimb of nude mice and grew as local solid tumors. After 4 weeks of TCHO tumor growth, plasma ionized calcium (Ca2+) increased to reach 1.48 +/- 0.03 mM (mean +/- SEM), whereas mice bearing similarly sized CCHO tumors and non-tumor-bearing mice (NTB) remained normocalcemic (normal range for Ca2+, 1.15-1.30 mM). Plasma TGF-alpha was undetectable by an ELIFA assay in all NTB mice, was markedly increased in all TCHO mice (5.75 +/- 0.78 ng/ml), and was slightly increased in CCHO mice (0.50 +/- 0.22 ng/ml). Quantitative bone histomorphometry showed a prominent increase in osteoclastic bone resorption in TCHO mice. These data suggest that TGF-alpha is a mediator of hypercalcemia and increased osteoclastic bone resorption in tumors that produce it in sufficient quantity.

Animals↗

[Severe hypocalcemia complicating outbreaks of renal failure in 2 uremic patients].

Hypocalcemia has many causes of which several often occur in combination in intensive care unit patients. Two cases (a 78-year-old male and a 63-year-old female) of severe hypocalcemia (corrected serum calcium 1.2 mmol/l in both cases) in patients hospitalized for acute decompensation of chronic renal failure are reported herein. Both subjects had a history of chronic hypocalcemia due to vitamin-calcium deficiencies and chronic renal failure. The lack of adverse clinical consequences of the low serum calcium levels can be explained by the fact that both patients also had severe metabolic acidosis, a disorder which increased the ionized fraction of total serum calcium. Serum calcium returned to normal slowly and gradually despite parenteral administration of large amounts of calcium and vitamin D or vitamin D derivatives.

Aged↗

Recruitment of new osteoblasts and osteoclasts is the earliest critical event in the pathogenesis of human multiple myeloma.

Considering the special relation of human multiple myeloma (MM) to bones, it is of importance to clarify the early steps of bone involvement in this disease. In this work, using bone histomorphometry (including histoenzymologic and kinetic studies for the first time), we have evaluated the bone remodeling (i.e., bone resorption and bone formation rates) of 16 individuals with early MM in comparison with that of 10 with benign monoclonal gammopathy (BMG) and that of 17 patients with previously untreated overt MM. A significantly increased osteoblastic recruitment was observed in the individuals with early MM when compared with those with BMG (P less than 0.01). A significant (P less than 0.01) increased bone resorption (i.e., eroded surfaces, osteoclast numbers and surfaces) was observed from the early stage of MM in comparison with the BMG status where bone resorption remained within the normal range. At the tissue level, there was no difference in terms of bone resorption between early and overt MM. On the other hand, osteoblast activity was significantly reduced in patients with overt MM (P less than 0.05 by comparison with those with early MM). A significant enhancement of osteoblastic recruitment with an increased generation of new osteoclasts is an early critical event in the pathogenesis of human MM. Of particular importance is the early stimulation of osteoblasts, since these cells produce high amounts of IL-6, a potent myeloma cell growth factor and a critical cytokine for the formation of osteoclasts in the bone marrow.

Bone Development↗