Approach in glucocorticoid-induced osteoporosis prevention: results from the Italian multicenter observational EGEO study.

Glucocorticoid-induced osteoporosis (GIO) is the most frequent cause of secondary osteoporosis. GIO is linked to glucocorticoids (GC) daily assumption with maximum effect within first months of treatment and decreasing to basal levels as the therapy is discontinued. In Italy, primary prevention of GIO is suggested when GC therapy (prednisone >5 mg/day or equivalent) is taken for longer than 3 months. Lazio GISMO (Italian Group for Study and Diagnosis of Bone Metabolism Diseases) group organized the GC and Osteoporosis Epidemiology study (EGEO) to evaluate physician's approach in preventing GIO. The study involved 19 osteoporosis centers. Patients taking long-term GC therapy were recruited and information collected: medical history and anthropometric data, GC therapy, primary disease, physician's specialty, osteopororosis screening, and pharmacological intervention. The study included 1334 patients. Mean age was 63 ± 13 yr; 243 (18%) patients had a history of falls from standing position in the previous 12 months, 78 (35%) vertebral fractures, 91 (41%) fractures other than vertebral, 27 (12%) femoral fractures, and 27 (12%) multiple sites fractures. The molecules of GC more often prescribed were prednisone and 6-metil prednisolone. One thousand and forty patients (78%) were taking GC for more than 6 months. GC therapy was prescribed more frequently by rheumatologists (62%). Antiosteoporotic drugs for GIO prevention were prescribed in 431 patients (32%). Among the patients, only 27% (360) received calcium and vitamin D supplements, and 39% (319) treated by rheumatologists received anti-resorptive drugs. In conclusion, our data show that in Italy, as already described elsewhere, only a small subpopulation of GC-treated patients was supported by an anti-osteoporotic therapy, indicating the need to further stimulate awareness of both patients and specialists, prescribing GC therapy, to an appropriate and prompt GIO prevention.

Chronic constipation in hypercalcemic patients with primary hyperparathyroidism.

BACKGROUND: Chronic constipation (C), among gastrointestinal symptoms, is commonly associated with primary hyperparathyroidism (PHPT) and probably attributable to hypercalcemia. OBJECTIVE OF THE STUDY: To evaluate in patients affected with PHPT the prevalence of C utilizing a validated questionnaire and the current prevalence of C compared to that observed in the past and to evaluate the relationship between C and the severity of PHPT. METHODS: 55 outpatients affected with PHPT, admitted to our Department of Internal Medicine and Medical Specialities in the years (2006-2009) were studied (group 1: 50 postmenopausal women and 5 men, mean age 61.9 +/- 9.4 years), together with 55 sex and age matched controls (group 2). Also considered were a group of PHPT patients observed, in the same ambulatory, during the years '70-'80 (group 3). A questionnaire, Rome II criteria, was administered and used to define C, whereas only anamneses were used to define C in group 3. RESULTS: The prevalence of C in patients with PHPT was 21.8% in group 1 vs 12.7% in group 2 (n.s.) and 32.7% in group 3. There is a decreasing trend in the prevalence of C in patients with PHPT as observed from 1970-89 to 2006-2009 (p < 0.05). The reduction of C was associated together with a significant reduction in the serum calcium level (p < 0.001). The presence of C vs its absence in patients with PHPT is characterized by higher values of calcemia (p < 0.001), ionized calcium (p < 0.001), and parathyroid hormone (p = 0.019). CONCLUSION: The actual prevalence of C in patients with PHPT is not significantly different from that found in the control group and is decreasing with respect to the past years. Moreover, C seems to be associated with the severity of the disease rather than with the diagnosis of PHPT per se.

Metabolic bone diseases during long-term total parenteral nutrition.

Long-term total parenteral nutrition (TPN) is a procedure commonly applied to patients with advanced forms of intestinal malabsorption. Among TPN complications, bone metabolic diseases, such as osteoporosis and osteomalacia, are a common finding. Initially considered to be a manifestation of aluminium toxicity which followed massive contamination with the element of the solutions used in TPN, metabolic osteopathy during TPN is currently considered a multiform syndrome, with a multifactorial pathogenesis, which may manifest itself with vague or clear clinical pictures. In this review, we analyse clinical, pathogenetic, and therapeutic aspects of the most common bone metabolic diseases in patients undergoing long-term TPN.

A new mathematical model based on clinical and laboratory variables for the diagnosis of Sjögren's syndrome.

Sjögren's syndrome (SS) is a systemic autoimmune disease that mainly affects exocrine glands. A diagnosis of SS in its early stages has a potential clinical relevance, but it is difficult and cannot be made solely on clinical grounds. Several sets of diagnostic criteria have been proposed, but none has met with a general consensus. Minor salivary gland has been judged to be the "gold standard" for the diagnosis of SS. However, it is a painful procedure and has a small but significant proportion of both false positive and false negative results. The aim of our study was to develop a simple mathematical score that uses clinical and laboratory variables for diagnosing SS, thereby reducing the need of minor salivary gland. The following variables were included in the model: ANA, SS-A/SS-B, Schirmer's Test/BUT, C3/C4, serum gammaglobulin levels. One hundred consecutive individuals reporting clinical syndromes consistent with a sicca syndrome were included in the study. The application of our multifactorial mathematical model has shown a high predictive value for SS vs controls or vs patients with other autoimmune disorders (Sensitivity 93%, Specificity 100%), with an estimated minor salivary gland reduction of 77%. We conclude that our mathematical model can be considered a useful non-invasive approach for diagnosing Sjogren's Syndrome and recommend its validation on a larger scale.

[Effects of the combined raloxifene-sodium fluoride therapy on bone mass and bone turnover in women with postmenopausal osteoporosis]. / Effetti della terapia combinata raloxifene-fluoruri sulla massa ossea e sul turnover scheletrico in donne affette da osteoporosi post-menopausale.

BACKGROUND: Aim of the study was to compare the effects of raloxifene (RLX) therapy alone or with a combination of RLX and slow release sodium fluoride (SRNaF) on bone mineral density (BMD) and bone turnover, at 1 year. METHODS: Ninety-two consecutive postmenopausal women with osteoporosis (49-62 yr old) were randomly allocated to a group A (n=48; RLX 60 mg/day per os) or a group B (n=44; RLX 60 mg/day per os plus SRNaF 25 mg x 2/day per os); all participants received oral calcium carbonate (500 mg x 2/day) and vitamin D3 (400 UI x 2/day) too. Lumbar spine (L1-L4) and femoral neck (FN) BMD were measured by dual energy X-ray absorptiometry (DEXA) at time 0 (T0), after 6 (T6) and 12 (T12) months; at the same time, serum bone specific alkaline phosphatase (BALP) and urinary N-terminal telopeptide of type I collagen normalized by creatinine (NTx/cr) were determined at T0, T6 and T12. RESULTS: Eighty-five women completed the study, 45 in group A and 40 in group B. In group B, after 1 year of treatment, we found a significant (p<0.01) increase in L1-L4 BMD (3.9+/-0.3%) respect to group A (2.8+/-0.1%); FN BMD in group B increased by 3.3+/-0.3% which was significantly different (p<0.01) from group A (2.3+/-0.1%), at 1 year. After 12 months of therapy, NTx/cr decreased significantly more (p<0.05) in group B (-36+/-2.6%) than group A (-29+/-2.0%); BALP levels increased in group B and decreased in group A: in group B BALP levels (11+/-1.2%) significantly increased (p<0.001) than group A (-2.1+/-0.1%), since 6th month. CONCLUSIONS: These data demonstrate that the combination of antiresorptive and bone-stimulating agents may dissociate bone resorption and bone formation and thus, by synergestic effect, induce a significative increase in BMD.

Relationship between serum albumin and bone mineral density in postmenopausal women and in patients with hypoalbuminemia.

Some discrepancies exist about the relationship between serum albumin level and the pathogenesis of osteoporosis; moreover, most of the studies available have especially concerned patients with osteoporosis, often associated with fractures. Our study, therefore, aims to investigate the presence of a relationship between serum albumin level and bone mineral density in a group of healthy women (n=650; mean age 59.0 +/- 7.4 years) who voluntarily underwent screening for osteoporosis only because they were menopausal (11.2 +/- 7.4 years since menopause) and, for comparison, in a group of outpatients (n = 44; mean age 57.6 +/- 7.0 years; 9.1 +/- 6.7 years since menopause) with hypoalbuminemia associated with diseases. The results show a lack of any relationship in healthy women between serum albumin value and bone mineral density; the lack of correlation was also shown when the postmenopausal women were down into normal, osteopenic and osteoporotic (WHO criteria) or in hypo, normal and hyperalbuminemic. The only significant parameters associated with lower bone mineral density, in fact, were age and years since menopause (p<0.0001 and p<0.0001 respectively at lumbar spine and p<0.02 and p<0.001 at femoral neck level). In the group of patients with hypoalbuminemia associated with diseases, on the other hand, a relationship between reduced bone mineral density and hypoalbuminemia was found (p<0.01 and p<0.05 respectively at lumbar spine and femoral neck). In conclusion, in healthy postmenopausal women the serum albumin level does not play a significant role in the pathogenesis of bone density reduction, which is mainly due to the number of years since menopause and advancing age. The hypoalbuminemia may be related to the reduction of bone mass only in the subjects affected by diseases associated with a significant albumin reduction.

Calcium homeostasis during oral glucose load in healthy women.

It has been demonstrated that in healthy subjects during oral glucose tolerance test, serum calcium declines, while urinary calcium excretion increases, even if there is not a general agreement in this regard. The study was carried out in order to evaluate the effects of glucose oral load on calcium homeostasis in eight healthy adult women, also considering ionized calcium, plasma insulin and parathyroid hormone changes. The results showed a decline of total and ionized serum calcium (p < 0.05 and p < 0.01, respectively; maximum of the decrease at time 120'), in parallel with the increase of urinary calcium/ creatinine ratio (p < 0.05). Serum glucose and insulin increase (p < 0.0001 and p < 0.0005 respectively; maximum value at time 60'), while the parathyroid hormone level decreases (maximum decline at time 120', p < 0.01). No changes were observed in fasting control subjects for all parameters considered. The changes of these parameters with time suggest that the effects of glucose oral load on calcium metabolism in healthy adult women may be the consequence of parathyroid hormone suppression induced by acute hyperglycemia/hyperinsulinemia. The results confirm in vivo the PTH behaviour in vitro, on cultured bovine parathyroid cells, with high glucose concentration.

[Drug-induced osteomalacia]. / Osteomalacia da farmaci.

The osteomalacia is a metabolic bone disease, characterized by a defect of bone mineralization, due to a lot of causes; among these an important role may be attributed to some drugs. The drugs most frequently associated with osteomalacia are: cholestyramine, phenytoin, phenobarbital, rifampicin, isoniazid, aluminium-containing antacid, saccharated ferric oxide, cadmium, lead, bisphosphonates, fluoride and aluminum. In this review we discuss about the pathophysiologic mechanisms related to drug-induced osteomalacia involving vitamin D metabolism, phosphorus homeostasis and bone mineralization.

Clinical and prognostic significance of hyperfibrinogenemia in cerebral ischemia.

In order to evaluate the clinical and prognostic significance of early hyperfibrinogenemia in patients with transient ischemic attack (TIA) and ischemic cerebral infarction (ICI), we analyzed the relationships between plasma fibrinogen, brain damage severity, clinical status on admission and intra-hospital mortality. Vascular damage severity was estimated by measuring the necrotic area by computed axial tomography (CT) and indirectly by means of changes in some plasma enzymes (CK, LDH, GPT/ALT, and GOT/AST). Plasma fibrinogen levels were statistically higher in ICI than in TIA and control subjects (p < 0.0005; analysis of variance). Moreover, plasma fibrinogen was directly related to the extension of the necrotic area at CT scan (p < 0.05) and in ICI patients was positively correlated with CK (r = 0.50, p < 0.01), LDH (r = 0.41, p < 0.05) and GOT/AST (r = 0.42, p < 0.05) serum levels, but not with GPT/ALT. A higher plasma fibrinogen value was observed in patients with stupor or coma compared with those with alert consciousness (p < 0.05). In patients who died during hospitalization, fibrinogen levels were higher than those of subjects who were discharged (p < 0.005). The results indicate that in the early phase of cerebral ischemia, plasma fibrinogen levels are related to the severity of the clinical status and to the extension of the brain vascular damage, thus representing a negative clinical and prognostic factor of the disease.

Acute serum calcium changes in transient ischemic attack and cerebral infarction.

Total (T-Ca), albumin corrected (A-Ca) and ionized (Ca++) serum calcium levels were measured in patients affected by transient ischemic attack (TIA) and ischemic cerebral infarction (ICI), in order to evaluate the clinical and prognostic significance of calcemic status during the acute phase of these events. These results demonstrate that the calcium level is decreased in cerebral ischemia and that more substantial changes are observed in ICI than in TIA and controls (p < 0.0001, p < 0.02 and p < 0.0001 respectively for T-Ca, A-Ca and Ca++; analysis of variance). The mean T-Ca was significantly reduced in patients who died during hospitalization compared with values observed in survivors (p < 0.005), whereas A-Ca and Ca++ were not different. The calcium changes observed in the early phase of TIA and ICI suggest that the severity of cerebral ischemia may condition the amount of its acute decrease. The cause of hypocalcemia is unclear (primary effect or secondary epiphenomenon of cerebral ischemia?), but when A-Ca and Ca++ are considered, its in-hospital unfavorable prognostic role may be excluded.

Serum albumin level at admission: mortality and clinical outcome in geriatric patients.

We evaluated serum albumin at time of admission, within 72 hours, in 135 geriatric patients who were older than 70 years to establish its role as a predictor of death and clinical outcome at time of discharge. Serum albumin values were reduced significantly in patients who died compared with those who were discharged in unchanged/impaired and improved conditions (3.01 +/- 0.68 g/dL, 3.18 +/- 0.55 g/dL, and 3.65 +/- 0.52 g/dL respectively, P < 0.0001). A correlation between serum albumin concentration at admission and number of days elapsed from admission and death was found (r = 0.43, P < 0.05). Mortality rate was 38.6% in patients with serum albumin values < 3.3 g/dL compared with 14.1% in those with albumin values > or = 3.3 g/dL (P < 0.005). Similar results were obtained even when the main diagnostic conditions, such as cardiocerebrovascular disease and cancer, were considered. The results demonstrate that in geriatric patients the serum albumin level at admission may be a predictor of mortality and clinical outcome at discharge.

One case of "prune belly" syndrome: prenatal and prognostic valuation.

A case of "Prune Belly" syndrome, its sonographic diagnosis, from the 15th week and its monitoring by sonography and biochemical exams of fetal urine for study of renal function is described. The good relation between prenatal prognosis and neonatal renal function is verified after birth.