Spine Fragility Fracture Prediction Using TBS and BMD in Postmenopausal Women: A Bayesian Approach.

The trabecular bone score (TBS) estimates bone microarchitecture and can be used to evaluate the risk of osteoporotic fractures independently of bone mineral density (BMD). In this retrospective case-control study, we tested and compared the ability of TBS and lumbar spine BMD (LS-BMD) to predict vertebral fragility fractures. The inclusion criteria were female sex, age range 50-90 years, menopause, and clinical risk factors for osteoporosis. Patients with secondary osteoporosis were excluded. LS-BMD and TBS were measured at the L1-L4 vertebral level. The ability of the two diagnostic systems in predicting vertebral fragility fractures was assessed by combining LS-BMD and TBS according to the Bayesian "OR rule" (the diagnosis is negative only for those negative for both tests, and it is positive for those who were positive for at least one test) or to the "AND rule" (the diagnosis is positive only for those positive to both tests and is negative for those negative for at least one test). Of the 992 postmenopausal women included, 86 had a documented vertebral fragility fracture. At the cutoff value used in the present study, the TBS and LS-BMD showed a similar diagnostic ability to predict vertebral fragility fractures, having positive predictive values (PPV) of, respectively, 13.19% and 13.24%. Negative predictive values (NPV) were, respectively, 95.40% and 94.95%. Compared to that of each single diagnostic system, the "OR-rule" significantly increased the NPV to 97.89%, while no statistically significant differences were found by using the "AND-rule". In conclusion, the present study highlights the possibility that combining LS-BMD and TBS could improve their predictive ability in diagnosing vertebral fragility fractures, and that there is a significant probability of absence of fractures in women who test negative to both diagnostic systems.

Citrate Supplementation Restores the Impaired Mineralisation Resulting from the Acidic Microenvironment: An In Vitro Study.

Chronic metabolic acidosis leads to bone-remodelling disorders based on excessive mineral matrix resorption and inhibition of bone formation, but also affects the homeostasis of citrate, which is an essential player in maintaining the acid-base balance and in driving the mineralisation process. This study aimed to investigate the impact of acidosis on the osteogenic properties of bone-forming cells and the effects of citrate supplementation in restoring the osteogenic features impaired by the acidic milieu. For this purpose, human mesenchymal stromal cells were cultured in an osteogenic medium and the extracellular matrix mineralisation was analysed at the micro- and nano-level, both in neutral and acidic conditions and after treatment with calcium citrate and potassium citrate. The acidic milieu significantly decreased the citrate release and hindered the organisation of the extracellular matrix, but the citrate supplementation increased collagen production and, particularly calcium citrate, promoted the mineralisation process. Moreover, the positive effect of citrate supplementation was observed also in the physiological microenvironment. This in vitro study proves that the mineral matrix organisation is influenced by citrate availability in the microenvironment surrounding bone-forming cells, thus providing a biological basis for using citrate-based supplements in the management of bone-remodelling disorders related to chronic low-grade acidosis.

Role of Citrate in Pathophysiology and Medical Management of Bone Diseases.

Citrate is an intermediate in the "Tricarboxylic Acid Cycle" and is used by all aerobic organisms to produce usable chemical energy. It is a derivative of citric acid, a weak organic acid which can be introduced with diet since it naturally exists in a variety of fruits and vegetables, and can be consumed as a dietary supplement. The close association between this compound and bone was pointed out for the first time by Dickens in 1941, who showed that approximately 90% of the citrate bulk of the human body resides in mineralised tissues. Since then, the number of published articles has increased exponentially, and considerable progress in understanding how citrate is involved in bone metabolism has been made. This review summarises current knowledge regarding the role of citrate in the pathophysiology and medical management of bone disorders.

Potassium Citrate Supplementation Decreases the Biochemical Markers of Bone Loss in a Group of Osteopenic Women: The Results of a Randomized, Double-Blind, Placebo-Controlled Pilot Study.

The relationship involving acid-base imbalance, mineral metabolism and bone health status has previously been reported but the efficacy of the alkalizing supplementation in targeting acid overload and preventing bone loss has not yet been fully elucidated. In this randomized, double-blind, placebo-controlled study, the hypothesis that potassium citrate (K citrate) modifies bone turnover in women with postmenopausal osteopenia was tested. Three hundred and ten women were screened; 40 women met the inclusion criteria and were randomly assigned to the treatment or the placebo group. They were treated with K citrate (30 mEq day-1) or a placebo in addition to calcium carbonate (500 mg day-1) and vitamin D (400 IU day-1). At baseline and time points of 3 and 6 months, serum indicators of renal function, electrolytes, calciotropic hormones, serum bone turnover markers (BTMs), tartrate-resistant acid phosphatase 5b (TRACP5b), carboxy-terminal telopeptide of type I collagen (CTX), bone alkaline phosphatase (BAP), procollagen type 1 N terminal propeptide (PINP)), and urine pH, electrolytes, and citrate were measured. The follow-up was completed by 17/20 patients in the "K citrate" group and 18/20 patients in the "placebo" group. At baseline, 90% of the patients exhibited low potassium excretion in 24 h urine samples, and 85% of cases had at least one urine parameter associated with low-grade acidosis (low pH, low citrate excretion). After treatment, CTX and BAP decreased significantly in both groups, but subjects with evidence of low-grade acidosis gained significant benefits from the treatment compared to the placebo. In patients with low 24h-citrate excretion at baseline, a 30% mean decrease in BAP and CTX was observed at 6 months. A significant reduction was also evident when low citrate (BAP: -25%; CTX: -35%) and a low pH (BAP: -25%; CTX: -30%) were found in fasting-morning urine. In conclusion, our results suggested that K citrate supplementation improved the beneficial effects of calcium and vitamin D in osteopenic women with a documented potassium and citrate deficit, and a metabolic profile consistent with low-grade acidosis.

The Trabecular Bone Score Predicts Spine Fragility Fractures in Postmenopausal Caucasian Women Without Osteoporosis Independently of Bone Mineral Density.

INTRODUCTION: The trabecular bone score (TBS) is a gray-level textural metric that can be extracted from the two-dimensional lumbar spine dual-energy X-ray absorptiometry (DXA) image. TBS is related to bone microarchitecture. Several literature data suggest that TBS predicts fracture risk as well as lumbar spine bone mineral density (LS-BMD) measurements in postmenopausal women. OBJECTIVE: A retrospective case-control study assessing the ability of the TBS to predict spine fragility fractures (SFF) in postmenopausal women with or without osteoporosis (diagnosed by T-score≤-2.5). METHODS: LS-BMD and the TBS were determined in the L1-L4 vertebrae. Statistical analyses were carried out in the entire group of women (entire-group) (n.699), in women both with osteoporosis (osteoporosis-subgroup) (n.253) and those without osteoporosis (non-osteoporosis-subgroup) (n. 446). RESULTS: At the unpaired t-test, both the TBS and the LS-BMD (p≤0.001) were lower in women with SFF (n.62) in the entire-group. In the non-osteoporosis subgroup, the TBS (p≤0.009) was lower in women with SFF (n.29). In the osteoporosis subgroup, the LS-BMD (p≤0.003) was lower in women with SFF (n.33). Considering the TBS and LS-BMD separately in a block logistic regression, the TBS was associated with SFF in the entire-group (odds ratio (OR): 1.599, 95% confidence interval (CI): 1.021-2.128) and in the non-osteoporosis-subgroup (OR: 1.725, 95% CI:1.118-2.660) whereas LS-BMD was associated with SFF in the entire-group (OR: 1.611, 95% CI: 1.187-2.187) and in the osteoporosis-subgroup (OR: 2.383, 95% CI: 1.135-5.003). According to forward logistic regression, entering the TBS, LS-BMD and confounders as predictors, the LS-BMD in the entire-group (OR: 1.620, 95% CI: 1.229-2.135) and in the osteoporosis subgroup (OR: 2.344, 95% CI: 1.194-4.600), and the TBS in the non-osteoporosis subgroup (OR: 1.685, 95% CI: 1.131-2.511) were the only predictors of SFFs. CONCLUSIONS: In the entire-group, the TBS predicted SFFs almost as well as LS-BMD, but not independently of it. The TBS, but not LS-BMD, predicted SFFs in the non-osteoporosis subgroup.

Assessment of Bone Quality in Osteoporosis Treatment with Bone Anabolic Agents: Really Something New?

Osteoporosis is a chronic pathologic condition, particularly of the elderly, in which a reduction of bone mineral density (BMD) weakens bone, leading to the so-called fragility fractures, most often of spine and femur. The gold standard exam for the quantitative measurement of BMD is the dual X-ray photon absorptiometry (DXA), a radiological method. However, a relevant number of fragility fractures occurs in the range of normal BMD values, meaning that also qualitative aspects of bone play a role, namely bone architecture and bone geometry. Bone structure is investigated by microCT and histomorphometry, which necessitate an invasive approach with a biopsy, usually taken at the iliac crest, not the typical site of fragility fractures. New tools, trabecular bone score (TBS) and hip structural analysis (HSA), obtained during DXA, can supply informations about bone structure of spine and femur, respectively, in a not invasive way. Therapy of osteoporosis is based on two types of drugs leading to an increase of BMD: antiresorptive and anabolic treatments. The antiresorptive drugs inhibit the osteoclasts, whereas teriparatide and, in part, strontium ranelate ameliorate bone structure. The present review deals with the relation between the anabolic drugs for osteoporosis and the cited new tools which investigate bone architecture and geometry, in order to clarify if they represent a real advantage in monitoring efficacy of osteoporosis' treatment. Data from the studies show that increases of TBS and HSA values after anabolic therapy are small and very close to their least significant change at the end of the usual period of treatment. Therefore, it is questionable if TBS and HSA are really helpful in monitoring bone quality and in defining reduction of individual fragility fracture risk during osteoporosis treatment with bone anabolic agents.

Potassium citrate prevents increased osteoclastogenesis resulting from acidic conditions: Implication for the treatment of postmenopausal bone loss.

The extracellular acidic milieu in bones results in activation of osteoclasts (OC) and inhibition of osteoblasts (OB) causing a net loss of calcium from the skeleton and the deterioration of bone microarchitecture. Alkalinization through supplementation with potassium citrate (K citrate) has been proposed to limit the osteopenia progression, even though its pharmacological activity in bone microenvironment is not well defined. We evaluated if K citrate was able to prevent the adverse effects that acidic milieu induces on bone cells. OC and OB were maintained in neutral (pH 7.4) versus acidic (pH 6.9) culture medium, and treated with different K citrate concentrations. We evaluated the OC differentiation at seven days, by counting of multinucleated cells expressing tartrate-resistant acid phosphatase, and the activity of mature OC at 14 days, by quantifying of collagen degradation. To evaluate the effects on OB, we analyzed proliferation, mineralization, and expression of bone-related genes. We found that the low pH increased OC differentiation and activity and decreased OB function. The osteoclastogenesis was also promoted by RANKL concentrations ineffective at pH 7.4. Non-cytotoxic K citrate concentrations were not sufficient to steadily neutralize the acidic medium, but a) inhibited the osteoclastogenesis, the collagen degradation, and the expression of genes involved in RANKL-mediated OC differentiation, b) enhanced OB proliferation and alkaline phosphatase expression, whereas it did not affect the in vitro mineralization, and c) were effective also in OC cultures resistant to alendronate, i.e. the positive control of osteoclastogenesis inhibition. In conclusion, K citrate prevents the increase in OC activity induced by the acidic microenvironment, and the effect does not depend exclusively on its alkalizing capacity. These data provide the biological basis for the use of K citrate in preventing the osteopenia progression resulting from low-grade acidosis.

Comparison of trabecular bone score and hip structural analysis with FRAX® in postmenopausal women with type 2 diabetes mellitus.

PURPOSE: To evaluate (a) the performance in predicting the presence of bone fractures of trabecular bone score (TBS) and hip structural analysis (HSA) in type 2 diabetic postmenopausal women compared to a control group and (b) the fracture prediction ability of TBS versus Fracture Risk Calculator (FRAX®) as well as whether TBS can improve the fracture prediction ability of FRAX® in diabetic women. METHODS: Eighty diabetic postmenopausal women were matched with 88 controls without major diseases for age and body mass index. The individual 10-year fracture risk was assessed by FRAX® tool for Europe-Italy; bone mineral density (BMD) at lumbar spine, femoral neck and total hip was evaluated through dual-energy X-ray absorptiometry; TBS measurements were taken using the same region of interest as the BMD measurements; HSA was performed at proximal femur with the HSA software. RESULTS: Regarding variables of interest, the only significant difference between diabetic and control groups was observed for the value of TBS (median value: 1.215; IQR 1.138-1.285 in controls vs. 1.173; IQR 1.082-1.217 in diabetic; p = 0.002). The prevalence of fractures in diabetic women was almost tripled than in controls (13.8 vs. 3.4 %; p = 0.02). The receiver operator characteristic curve analysis showed that TBS alone (AUC = 0.71) had no significantly lower discriminative power for fracture prediction in diabetic women than FRAX major adjusted for TBS (AUC = 0.74; p = 0.65). CONCLUSION: In diabetic postmenopausal women TBS is an excellent tool in identifying fragility fractures.

Dietary treatment of urinary risk factors for renal stone formation. A review of CLU Working Group.

OBJECTIVE: Diet interventions may reduce the risk of urinary stone formation and its recurrence, but there is no conclusive consensus in the literature regarding the effectiveness of dietary interventions and recommendations about specific diets for patients with urinary calculi. The aim of this study was to review the studies reporting the effects of different dietary interventions for the modification of urinary risk factors in patients with urinary stone disease. MATERIALS AND METHODS: A systematic search of the Pubmed database literature up to July 1, 2014 for studies on dietary treatment of urinary risk factors for urinary stone formation was conducted according to a methodology developed a priori. Studies were screened by titles and abstracts for eligibility. Data were extracted using a standardized form and the quality of evidence was assessed. RESULTS: Evidence from the selected studies were used to form evidence-based guideline statements. In the absence of sufficient evidence, additional statements were developed as expert opinions. CONCLUSIONS: General measures: Each patient with nephrolithiasis should undertake appropriate evaluation according to the knowledge of the calculus composition. Regardless of the underlying cause of the stone disease, a mainstay of conservative management is the forced increase in fluid intake to achieve a daily urine output of 2 liters. HYPERCALCIURIA: Dietary calcium restriction is not recommended for stone formers with nephrolithiasis. Diets with a calcium content ≥ 1 g/day (and low protein-low sodium) could be protective against the risk of stone formation in hypercalciuric stone forming adults. Moderate dietary salt restriction is useful in limiting urinary calcium excretion and thus may be helpful for primary and secondary prevention of nephrolithiasis. A low-normal protein intake decrease calciuria and could be useful in stone prevention and preservation of bone mass. Omega-3 fatty acids and bran of different origin decreases calciuria, but their impact on the urinary stone risk profile is uncertain. Sports beverage do not affect the urinary stone risk profile. HYPEROXALURIA: A diet low in oxalate and/or a calcium intake normal to high (800-1200 mg/day for adults) reduce the urinary excretion of oxalate, conversely a diet rich in oxalates and/or a diet low in calcium increase urinary oxalate. A restriction in protein intake may reduce the urinary excretion of oxalate although a vegetarian diet may lead to an increase in urinary oxalate. Adding bran to a diet low in oxalate cancels its effect of reducing urinary oxalate. Conversely, the addition of supplements of fruit and vegetables to a mixed diet does not involve an increased excretion of oxalate in the urine. The intake of pyridoxine reduces the excretion of oxalate. HYPERURICOSURIA: In patients with renal calcium stones the decrease of the urinary excretion of uric acid after restriction of dietary protein and purine is suggested although not clearly demonstrated. HYPOCITRATURIA: The administration of alkaline-citrates salts is recommended for the medical treatment of renal stone-formers with hypocitraturia, although compliance to this treatment is limited by gastrointestinal side effects and costs. Increased intake of fruit and vegetables (excluding those with high oxalate content) increases citrate excretion and involves a significant protection against the risk of stone formation. Citrus (lemons, oranges, grapefruit, and lime) and non citrus fruits (melon) are natural sources of dietary citrate, and several studies have shown the potential of these fruits and/or their juices in raising urine citrate levels. CHILDREN: There are enought basis to advice an adequate fluid intake also in children. Moderate dietary salt restriction and implementation of potassium intake are useful in limiting urinary calcium excretion whereas dietary calcium restriction is not recommended for children with nephrolithiasis. It seems reasonable to advice a balanced consumption of fruit and vegetables and a low consumption of chocolate and cola according to general nutritional guidelines, although no studies have assessed in pediatric stone formers the effect of fruit and vegetables supplementation on urinary citrate and the effects of chocolate and cola restriction on urinary oxalate in pediatric stone formers. Despite the low level of scientific evidence, a low-protein (< 20 g/day) low-salt (< 2 g/day) diet with high hydration (> 3 liters/day) is strongly advised in children with cystinuria. ELDERLY: In older patients dietary counseling for renal stone prevention has to consider some particular aspects of aging. A restriction of sodium intake in association with a higher intake of potassium, magnesium and citrate is advisable in order to reduce urinary risk factors for stone formation but also to prevent the loss of bone mass and the incidence of hypertension, although more hemodynamic sensitivity to sodium intake and decreased renal function of the elderly have to be considered. A diet rich in calcium (1200 mg/day) is useful to maintain skeletal wellness and to prevent kidney stones although an higher supplementation could involve an increase of risk for both the formation of kidney stones and cardiovascular diseases. A lower content of animal protein in association to an higher intake of plant products decrease the acid load and the excretion of uric acid has no particular contraindications in the elderly patients, although overall nutritional status has to be preserved.

Utility of the trabecular bone score (TBS) in secondary osteoporosis.

Altered bone micro-architecture is an important factor in accounting for fragility fractures. Until recently, it has not been possible to gain information about skeletal microstructure in a way that is clinically feasible. Bone biopsy is essentially a research tool. High-resolution peripheral Quantitative Computed Tomography, while non-invasive, is available only sparsely throughout the world. The trabecular bone score (TBS) is an imaging technology adapted directly from the Dual Energy X-Ray Absorptiometry (DXA) image of the lumbar spine. Thus, it is potentially readily and widely available. In recent years, a large number of studies have demonstrated that TBS is significantly associated with direct measurements of bone micro-architecture, predicts current and future fragility fractures in primary osteoporosis, and may be a useful adjunct to BMD for fracture detection and prediction. In this review, we summarize its potential utility in secondary causes of osteoporosis. In some situations, like glucocorticoid-induced osteoporosis and in diabetes mellitus, the TBS appears to out-perform DXA. It also has apparent value in numerous other disorders associated with diminished bone health, including primary hyperparathyroidism, androgen-deficiency, hormone-receptor positive breast cancer treatment, chronic kidney disease, hemochromatosis, and autoimmune disorders like rheumatoid arthritis. Further research is both needed and warranted to more clearly establish the role of TBS in these and other disorders that adversely affect bone.

Decreased transcriptional activity of calcium-sensing receptor gene promoter 1 is associated with calcium nephrolithiasis.

BACKGROUND: CaSR gene is a candidate for calcium nephrolithiasis. Single-nucleotide polymorphisms (SNPs) encompassing its regulatory region were associated with calcium nephrolithiasis. AIMS: We tested SNPs in the CaSR gene regulatory region associated with calcium nephrolithiasis and their effects in kidney. SUBJECTS AND METHODS: One hundred sixty-seven idiopathic calcium stone formers and 214 healthy controls were genotyped for four CaSR gene SNPs identified by bioinformatics analysis as modifying transcription factor binding sites. Strontium excretion after an oral load was tested in 55 stone formers. Transcriptional activity induced by variant alleles at CaSR gene promoters was compared by luciferase reporter gene assay in HEK-293 and HKC-8 cells. CaSR and claudin-14 mRNA levels were measured by real-time PCR in 107 normal kidney medulla samples and compared in patients with different CaSR genotype. RESULTS: Only rs6776158 (A>G), located in the promoter 1, was associated with nephrolithiasis. Its minor G allele was more frequent in stone formers than controls (37.8% vs 26.4%, P = .001). A reduced strontium excretion was observed in GG homozygous stone formers. Luciferase fluorescent activity was lower in cells transfected with the promoter 1 including G allele at rs6776158 than cells transfected with the A allele. CaSR mRNA levels were lower in kidney medulla samples from homozygous carriers for the G allele at rs6776158 than carriers for the A allele. Claudin-14 mRNA levels were also lower in GG homozygous subjects. CONCLUSIONS: Minor allele at rs6776158 may predispose to calcium stones by decreasing transcriptional activity of the CaSR gene promoter 1 and CaSR expression in kidney tubules.

Predicting five-year recurrence rates of kidney stones: an artificial neural network model.

OBJECTIVE: Due to high recurrence rates of urolithiasis, many attempts have been performed to identify tools for predicting the risk of stone formation. The application of Artificial Neural Networks (ANNs) seems to be a valid candidate for reaching this endpoint. The aim of this study was to find a set of parameters able to predict recurrence episodes immediately after clinical and metabolic evaluation performed at the first visit in a 5-year window. MATERIAL AND METHODS: Data were collected from 80 outpatients who presented idiopathic calcium stone disease both at baseline and after 5 years; patients underwent treatment including both general measures and medical therapy. After 5 years, patients were classified into two subsets, namely SSFs (without recurrence episodes), consisting of 45 subjects (56.25%) and RSFs, with at least one episode of recurrence after the baseline, consisting of 35 subjects (43.75%). Helped by conventional statistics (One-way ANOVA and three Discriminant Analyses: standard, backward stepwise and forward stepwise), an Artificial Neural Network (ANN) approach was used to predict recurrence episodes. RESULTS: An optimal set of 6 parameters was identified from amongst the different combinations in order to efficiently predict the outcome of stone recurrence in approximately 90% of cases. This set consist of serum Na and K as well as Na, P, Oxalate and AP (CaP) index from urine. The results obtained with ANN seem to suggest that some kind of relationship is present between the identified parameters and future stone recurrence. This relationship is probably very complex (in the mathematical sense) and non-linear In fact, a Logistic Regression was built as a comparative method and performed less good results at least in terms of accuracy and sensitivity. CONCLUSIONS: The application of ANN to the database led to a promising predicting algorithm and suggests that a strongly non-linear relationship seems to exist between the parameters and the recurrence episodes. In particular, the ANN approach identifies as optimal parameters serum concentration of Na and K as well as urinary excretion of Na, P, Oxalate and AP (CaP) index. This study suggest that ANNs could potentially be a useful approach because of their ability to work with complex dynamics such as recurrent stone formation seems to have.

[Diagnostic and therapeutic approach in patients with urinary calculi]. / Percorso diagnostico-terapeutico per il paziente con calcolosi urinaria.

The natural history of urolithiasis includes the risk of recurrence and of the development of chronic kidney and/or bone disease, which is why a thorough clinical and metabolic evaluation of these patients is of the utmost importance at disease onset. This paper is aimed at identifying the type of urolithiasis, the related risk factors, and the corresponding treatment options. The diagnostic and therapeutic approach described here includes 1) accurate history taking to detect secondary nephrolithiasis and screen for the main risk factors for kidney and bone disease; 2) metabolic evaluation graded according to different complexity levels based on the severity of the disease and the presence of risk factors; 3) carrying out appropriate imaging procedures. The resulting information allows to plan treatment based either on general rules of lifestyle and diet, or on selected medical intervention, if necessary. This report, which is based on current guidelines, was produced by the Gruppo Italiano di Studio Multidisciplinare per la Calcolosi Renale. It is addressed to all professionals involved in the management of patients suffering from nephrolithiasis, first of all general practitioners, who often become involved immediately at the onset of the disease.

Urinary citrate and renal stone disease: the preventive role of alkali citrate treatment.

Hypocitraturia or low urinary citrate excretion is a common feature in patients with nephrolithiasis, particularly in those with calcium stone disease. Citrate is a weak acid that is synthesized inside Krebs' cycle. It can also enter the body through dietary intake. Differences in intestinal handling, serum concentration as well as filtered load of citrate were not found between kidney stone formers and normal subjects. On the contrary, several metabolic abnormalities, such as metabolic acidosis, hypokalemia and starving, seem to influence the renal handling of citrate by inducing a decrease in the urinary citrate excretion. Hypocitraturia is defined as urinary citrate excretion lower than 320 mg/day. Literature data show a large prevalence of hypocitraturia in patients with nephrolithiasis, ranging from 8% up to 68.3%. The protective role of citrate is linked to several mechanisms; in fact citrate reduces urinary supersaturation of calcium salts by forming soluble complexes with calcium ions and by inhibiting crystal growth and aggregation. Furthermore, citrate increases the activity of some macromolecules in the urine (eg. Tamm-Horsfall protein) that inhibit calcium oxalate aggregation. Citrate seems able to reduce the expression of urinary osteopontin. A role of citrate in pathogenesis of metabolic bone diseases has been recently suggested and citrate measurement in urine has been proposed as a predictor of both bone mass loss and fracture risk. Idiopathic calcium stone disease, with or without hypocitraturia, can be treated with alkaline citrate, as well as other forms of nephrolithiasis and different pathological conditions. The therapy with potassium citrate, or magnesium potassium citrate, is commonly prescribed in clinical practice in order to increase urinary citrate and to reduce stone formation rates. Our data as well as those of the literature confirm that alkali citrate induces both an increase of protective urinay analytes (eg. citrate, potassium and pH) and a decrease of calcium oxalate supersaturation. Moreover, alkali treatment reduces the rate of stone recurrence and increases the clearance rates and dissolution of stone fragments. Last but not the least, an increasing number of papers pointed out the protective role of alkali citrate in preserving bone mass in stone formers as well as in healthy subjects with bone loss. Nevertheless, the evaluation of urinary citrate in patients with kidney stones and the treatment of these patients with alkali salts namely with potassium citrate are still scarce.

RANKL/OPG/TRAIL plasma levels and bone mass loss evaluation in antiretroviral naive HIV-1-positive men.

Osteopenia and osteoporosis are common in HIV-1-infected individuals and represent a challenge in clinical and therapeutic management. This report investigated osteopenia/osteoporosis in a group of 31 antiretroviral naive HIV-1-positive men and the role of specific molecules belonging to TNF and the TNF-receptor family in HIV-1-related bone mass loss. Osteoprotegerin (OPG), the receptor activator of NF-kappab-ligand (RANKL), and the TNF-related apoptosis-inducing ligand (TRAIL) were significantly increased in the plasma of antiretroviral naive HIV-1-positive patients compared to a control group of healthy blood donors. In addition, TRAIL and RANKL plasma concentrations were positively correlated to HIV-1-RNA viral load. Measurement of bone mineral density in 20 out of 31 HIV-1-positive subjects disclosed osteopenia/osteoporosis in 40% of these patients. The antiretroviral naive HIV-1-positive subjects with low bone mineral density had a decreased plasma OPG/RANKL ratio and a plasma RANKL concentration >500 pg/ml. Together, these data indicate that plasma concentrations of specific factors involved in bone homeostasis were increased during HIV-1 infection and that RANKL and OPG/RANKL ratio deregulation may be involved in osteopenia/osteoporosis occurring in antiretroviral naive HIV-1 individuals.

Morphometric dual-energy X-ray absorptiometry (MXA) for identification of vertebral fractures.

Visual identification of vertebral fractures from spinal radiographs makes use of operator expertise in ruling out non-fracture deformities or normal variants. Morphometric X-ray absorptiometry (MXA) has recently been developed to assess vertebral deformity status quantitatively by dual energy X-ray absorptiometry (DXA). The reliability of MXA measurements depends on the precision of the technique, and this is influenced by system error, variability associated with morphometric analysis, and variability within study populations. This technique has proved to be useful in the identification and evaluation of osteoporotic vertebral deformities in both epidemiologic surveys and clinical trials. The major limitation of DXA vertebral assessment is the poor quality of images of thoracic vertebrae. We conclude that, used as a screening tool, this approach may help to identify vertebral fractures with a reduced radiation dose to the patient, and that technological improvements are necessary to improve image quality.

Citrate and mineral metabolism: kidney stones and bone disease.

Citrate is a weak acid that is formed in the tricarboxylic acid cycle or that may be introduced with diet. In the present paper all the mechanisms involved in intestinal absorption, renal handling and modulation of citrate will be reviewed. The evaluation of plasma citric acid is scarcely used in the diagnosis of human diseases. On the contrary urinary citrate excretion is a common tool in the differential diagnosis of kidney stones, renal tubular acidosis and it plays also a role in bone diseases. Therefore the importance of hypocitraturia will be reviewed with regard to bone mass, urine crystallization and urolithiasis. Finally particular attention will be paid to the incidence of hypocitraturia and to the therapy with citrate salts, both in kidney stone disease and in osteopenia.