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

Aspetti epidemiologici della calcolosi di calcio in Italia: distribuzione dei fenotipi intermedi nella popolazione italiana

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Citrates in nephrolithiasis

Nephrolithiasis is a multisystem disease arising from the sin- ergic effects of enviromental, hormonal and genetic factors. In Europe an incidence of 2000 stones per million of population has been reported. Kidney stones are mainly composed of calcium (70-80%) with a predominance of calcium oxalate, with or without calcium phosphate. Low urinary citrate excre- tion is a common feature of idiopathic calcium stone disease. A wide range of hypocitraturia prevalence in nephrolithiasis have been reported in literature. Hypocitraturia is defined as a urinary citrate excretion lower than 320 mg/day. Many factors can modulate citrate excretion. Among them an important role is played by acid-base status, nutritional factors, strarvation, hormones and drugs. Estrogen exert an important modulating effect on urinary citrate excretion. Several authors, in fact, have described a reduction in urinary citrate excretion in healthy postmenopausal women, as well as a lower citraturia in males than in premenopausal females. Urinary citrate di- rectly inhibits stone formation by forming highly soluble com- plexes with calcium in the renal tubule and by increasing in- traluminal pH. Idiopathic calcium stone disease, but also other forms of nephrolithiasis, as well as some other pathological conditions can be treated with alkaline citrate. The most com- mon form of these salts is potassium citrate that has been successfully used in the prevention of stone ecurrence. In conclusion alkaline citrate represents an effective tool in the prevention of calcium stone formation. Last, but not least, this form of therapy presents few side effect

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

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

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

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

Effect of K citrate on OC cultures resistant to alendronate under the effect of acidic microenvironment.

<p>Data are expressed as total number of OC counted in eight separate experiments. The OC cultures react differently to the alendronate in neutral (<b>A</b>) or acidic (<b>B</b>) culture medium. The red lines highlight two cultures which were resistant to the anti-osteoclastogenic effect of Ale 10⁻⁵. The <b>C</b> and <b>D</b> graphs show the data of three separate experiments (#1; #2; #3) exposed to Ale 10⁻⁵ (<b>C</b>) and Ale 10⁻⁶ (<b>D</b>), supplemented with K citrate (0 mM, 0.15 mM, 0.3 mM). Results are expressed as a ratio between number of OC treated with different concentrations of K citrate/ alendronate, and number of OC counted in the negative control, i.e. K citrate 0 mM, Ale 0 mM, pH 6.9. The red line is the OC culture resistant to Ale 10⁻⁵ (#2), and representative images are shown in the panel <b>E</b>. The dashed line is the OC culture which is stimulated by Ale 10⁻⁶ (#3), and the pictures below highlight the effect of K citrate (<b>F</b>). OC are the cells with more than three nuclei and red staining of cytoplasm (positive reaction to TRAP). The arrows indicate small and large OC. KC is K citrate. Magnification x 20, Scale bar = 50 μm.</p