Postgraduate Symposium: Positive influence of nutritional alkalinity on bone health.

There is growing evidence that consumption of a Western diet is a risk factor for osteoporosis through excess acid supply, while fruits and vegetables balance the excess acidity, mostly by providing K-rich bicarbonate-rich foods. Western diets consumed by adults generate approximately 50-100 mEq acid/d; therefore, healthy adults consuming such a diet are at risk of chronic low-grade metabolic acidosis, which worsens with age as a result of declining kidney function. Bone buffers the excess acid by delivering cations and it is considered that with time an overstimulation of this process will lead to the dissolution of the bone mineral content and hence to reduced bone mass. Intakes of K, Mg and fruit and vegetables have been associated with a higher alkaline status and a subsequent beneficial effect on bone health. In healthy male volunteers an acid-forming diet increases urinary Ca excretion by 74% and urinary C-terminal telopeptide of type I collagen (C-telopeptide) excretion by 19% when compared with an alkali (base-forming) diet. Cross-sectional studies have shown that there is a correlation between the nutritional acid load and bone health measured by bone ultrasound or dual-energy X-ray absorptiometry. Few studies have been undertaken in very elderly women (>75 years), whose osteoporosis risk is very pertinent. The EVAluation of Nutrients Intakes and Bone Ultra Sound Study has developed and validated (n 51) an FFQ for use in a very elderly Swiss population (mean age 80.4 (sd 2.99) years), which has shown intakes of key nutrients (energy, fat, carbohydrate, Ca, Mg, vitamin C, D and E) to be low in 401 subjects. A subsequent study to assess net endogenous acid production (NEAP) and bone ultrasound results in 256 women aged > or = 75 years has shown that lower NEAP (P=0.023) and higher K intake (P=0.033) are correlated with higher bone ultrasound results. High acid load may be an important additional risk factor that may be particularly relevant in very elderly patients with an already-high fracture risk. The latter study adds to knowledge by confirming a positive link between dietary alkalinity and bone health indices in the very elderly. In a further study to complement these findings it has also been shown in a group of thirty young women that in Ca sufficiency an acid Ca-rich water has no effect on bone resorption, while an alkaline bicarbonate-rich water leads to a decrease in both serum parathyroid hormone and serum C-telopeptide. Further investigations need to be undertaken to study whether these positive effects on bone loss are maintained over long-term treatment. Mineral-water consumption could be an easy and inexpensive way of helping to prevent osteoporosis and could be of major interest for long-term prevention of bone loss.

PTH and 1.25 vitamin D response to a low-calcium diet is associated with bone mineral density in renal stone formers.

BACKGROUND: Renal calcium stones and hypercalciuria are associated with a reduced bone mineral density (BMD). Therefore, the effect of changes in calcium homeostasis is of interest for both stones and bones. We hypothesized that the response of calciuria, parathyroid hormone (PTH) and 1.25 vitamin D to changes in dietary calcium might be related to BMD. METHODS: A single-centre prospective interventional study of 94 hyper- and non-hypercalciuric calcium stone formers consecutively retrieved from our stone clinic. The patients were investigated on a free-choice diet, a low-calcium diet, while fasting and after an oral calcium load. Patient groups were defined according to lumbar BMD (z-score) obtained by dual X-ray absorptiometry (group 1: z-score <-0.5, n = 30; group 2: z-score -0.5-0.5, n = 36; group 3: z-score >0.5, n = 28). The effect of the dietary interventions on calciuria, 1.25 vitamin D and PTH in relation to BMD was measured. RESULTS: An inverse relationship between BMD and calciuria was observed on all four calcium intakes (P = 0.009). On a free-choice diet, 1.25 vitamin D and PTH levels were identical in the three patient groups. However, the relative responses of 1.25 vitamin D and PTH to the low-calcium diet were opposite in the three groups with the highest increase of 1.25 vitamin D in group 1 and the lowest in group 3, whereas PTH increase was most pronounced in group 3 and least in group 1. CONCLUSION: Calcium stone formers with a low lumbar BMD exhibit a blunted response of PTH release and an apparently overshooting production of 1.25 vitamin D following a low-calcium diet.

Prediction of 18-month survival in patients with primary myelodysplastic syndrome. A regression model and scoring system based on the combination of chromosome findings and the Bournemouth score.

The predictive potential of six selected factors was assessed in 72 patients with primary myelodysplastic syndrome using univariate and multivariate logistic regression analysis of survival at 18 months. Factors were age (above median of 69 years), dysplastic features in the three myeloid bone marrow cell lineages, presence of chromosome defects, all metaphases abnormal, double or complex chromosome defects (C23), and a Bournemouth score of 2, 3, or 4 (B234). In the multivariate approach, B234 and C23 proved to be significantly associated with a reduction in the survival probability. The similarity of the regression coefficients associated with these two factors means that they have about the same weight. Consequently, the model was simplified by counting the number of factors (0, 1, or 2) present in each patient, thus generating a scoring system called the Lausanne-Bournemouth score (LB score). The LB score combines the well-recognized and easy-to-use Bournemouth score (B score) with the chromosome defect complexity, C23 constituting an additional indicator of patient outcome. The predicted risk of death within 18 months calculated from the model is as follows: 7.1% (confidence interval: 1.7-24.8) for patients with an LB score of 0, 60.1% (44.7-73.8) for an LB score of 1, and 96.8% (84.5-99.4) for an LB score of 2. The scoring system presented here has several interesting features. The LB score may improve the predictive value of the B score, as it is able to recognize two prognostic groups in the intermediate risk category of patients with B scores of 2 or 3. It has also the ability to identify two distinct prognostic subclasses among RAEB and possibly CMML patients. In addition to its above-described usefulness in the prognostic evaluation, the LB score may bring new insights into the understanding of evolution patterns in MDS. We used the combination of the B score and chromosome complexity to define four classes which may be considered four possible states of myelodysplasia and which describe two distinct evolutional pathways.

Repair of tracheomalacia with inflammatory defect and mediastinitis.

We describe a novel repair of an anterior inflammatory tracheal defect with mediastinitis, which occurred after external tracheal suspension of localized intrathoracic tracheomalacia. The malacic tracheal segment of 4-cm length containing the inflammatory tracheal defect was noncircumferentially resected. A temporary endotracheal silicone stent was introduced, and the trachea was closed by a pedicled pectoralis muscle flap reinforced with an embedded rib segment. Retrieval of the stent 5 months postoperatively resulted in a re-epithelialized, persistently stable, noncollapsible tracheal segment that showed the same diameter and configuration as the nonreconstructed part of the trachea.

Effects of zoledronate versus placebo on spine bone mineral density and microarchitecture assessed by the trabecular bone score in postmenopausal women with osteoporosis: A three-year study.

The trabecular bone score (TBS) is an index of bone microarchitectural texture calculated from anteroposterior dual-energy X-ray absorptiometry (DXA) scans of the lumbar spine (LS) that predicts fracture risk, independent of bone mineral density (BMD). The aim of this study was to compare the effects of yearly intravenous zoledronate (ZOL) versus placebo (PLB) on LS BMD and TBS in postmenopausal women with osteoporosis. Changes in TBS were assessed in the subset of 107 patients recruited at the Department of Osteoporosis of the University Hospital of Berne, Switzerland, who were included in the HORIZON trial. All subjects received adequate calcium and vitamin D3. In these patients randomly assigned to either ZOL (n = 54) or PLB (n = 53) for 3 years, BMD was measured by DXA and TBS assessed by TBS iNsight (v1.9) at baseline and 6, 12, 24, and 36 months after treatment initiation. Baseline characteristics (mean ± SD) were similar between groups in terms of age, 76.8 ± 5.0 years; body mass index (BMI), 24.5 ± 3.6 kg/m(2) ; TBS, 1.178 ± 0.1 but for LS T-score (ZOL-2.9 ± 1.5 versus PLB-2.1 ± 1.5). Changes in LS BMD were significantly greater with ZOL than with PLB at all time points (p < 0.0001 for all), reaching +9.58% versus +1.38% at month 36. Change in TBS was significantly greater with ZOL than with PLB as of month 24, reaching +1.41 versus-0.49% at month 36; p = 0.031, respectively. LS BMD and TBS were weakly correlated (r = 0.20) and there were no correlations between changes in BMD and TBS from baseline at any visit. In postmenopausal women with osteoporosis, once-yearly intravenous ZOL therapy significantly increased LS BMD relative to PLB over 3 years and TBS as of 2 years. © 2013 American Society for Bone and Mineral Research.

Bone marrow dosimetry in rats using direct tissue counting after injection of radio-iodinated intact monoclonal antibodies or F(ab')2 fragments.

Normal rats were injected intravenously with 131I- and 125I-labeled intact murine and chimeric mouse-human monoclonal antibodies directed against carcinoembryonic antigen or with the corresponding F(ab')2 fragments. At different times after injection, individual animals were killed and radioactivity of blood and major organs, including bones and bone marrow, was determined. Ratios comparing radioactivity concentration in different tissues with that of bone marrow were calculated and found to remain stable during several effective half-lives of the antibodies. Mean bone marrow radioactivity was 35% (range, 29%-40%) of that of blood and 126% (range, 108%-147%) of that of liver after injection of intact Mabs or F(ab')2 fragments. In nude rats bearing human colon carcinoma xenografts producing carcinoembryonic antigen, relative bone marrow radioactivity was slightly lower than that in normal rats.

Influence of segmental chromosome abnormalities on survival in children over the age of 12 months with unresectable localised peripheral neuroblastic tumours without MYCN amplification.

BACKGROUND: The prognostic impact of segmental chromosome alterations (SCAs) in children older than 1 year, diagnosed with localised unresectable neuroblastoma (NB) without MYCN amplification enrolled in the European Unresectable Neuroblastoma (EUNB) protocol is still to be clarified, while, for other group of patients, the presence of SCAs is associated with poor prognosis. METHODS: To understand the role of SCAs we performed multilocus/pangenomic analysis of 98 tumour samples from patients enrolled in the EUNB protocol. RESULTS: Age at diagnosis was categorised into two groups using 18 months as the age cutoff. Significant difference in the presence of SCAs was seen in tumours of patients between 12 and 18 months and over 18 months of age at diagnosis, respectively (P=0.04). A significant correlation (P=0.03) was observed between number of SCAs per tumour and age. Event-free (EFS) and overall survival (OS) were calculated in both age groups, according to both the presence and number of SCAs. In older patients, a poorer survival was associated with the presence of SCAs (EFS=46% vs 75%, P=0.023; OS=66.8% vs 100%, P=0.003). Moreover, OS of older patients inversely correlated with number of SCAs (P=0.002). Finally, SCAs provided additional prognostic information beyond histoprognosis, as their presence was associated with poorer OS in patients over 18 months with unfavourable International Neuroblastoma Pathology Classification (INPC) histopathology (P=0.018). CONCLUSIONS: The presence of SCAs is a negative prognostic marker that impairs outcome of patients over the age of 18 months with localised unresectable NB without MYCN amplification, especially when more than one SCA is present. Moreover, in older patients with unfavourable INPC tumour histoprognosis, the presence of SCAs significantly affects OS.

PPAR gamma: ally and foe in bone metabolism.

Bone homeostasis is a well-balanced process that is largely dependent on the contribution of both bone-forming osteoblasts and bone-resorbing osteoclasts. A new study (Wan et al., 2007) suggests a previously unsuspected role for the transcription factor PPARgamma in promoting bone progenitors to the osteoclastic lineage.

Revision anterior cruciate ligament reconstruction with quadriceps tendon-patellar bone autograft.

PURPOSE: To evaluate the cause of recurrent pathologic instability after anterior cruciate ligament (ACL) surgery and the effectiveness of revision reconstruction using a quadriceps tendon autograft using a 2-incision technique. TYPE OF STUDY: Retrospective follow-up study. METHODS: Between 1999 and 2001, 31 patients underwent ACL revision reconstruction because of recurrent pathologic instability during sports or daily activities. Twenty-eight patients were reviewed after a mean follow-up of 4.2 years (range, 3.3 to 5.6 years). The mean age at revision surgery was 27 years (range, 18 to 41 years). The average time from primary procedure to revision surgery was 26 months (range, 9 to 45 months). A clinical, functional, and radiographic evaluation was performed. Also magnetic resonance imaging (MRI) or computed tomography (CT) scanning was performed. The International Knee Documentation Committee (IKDC), Lysholm, and Tegner scales were used. A KT-1000 arthrometer measurement (MEDmetric, San Diego, CA) by an experienced physician was made. RESULTS: Of the failures, 79% had radiographic evidence of malposition of their tunnels. In only 6 cases (21%) was the radiologic anatomy of tunnel placement judged to be correct on both the femoral and tibial side. The MRI or CT showed, in 6 cases, a too-centrally placed femoral tunnel. After revision surgery, the position of tunnels was corrected. A significant improvement of Lachman and pivot-shift phenomenon was observed. In particular, 17 patients had a negative Lachman test, and 11 patients had a grade I Lachman with a firm end point. Preoperatively, the pivot-shift test was positive in all cases, and at last follow-up in 7 patients (25%) a grade 1+ was found. Postoperatively, KT-1000 testing showed a mean manual maximum translation of 8.6 mm (SD, 2.34) for the affected knee; 97% of patients had a maximum manual side-to-side translation <5 mm. At the final postoperative evaluation, 26 patients (93%) graded their knees as normal or nearly normal according to the IKDC score. The mean Lysholm score was 93.6 (SD, 8.77) and the mean Tegner activity score was 6.1 (SD, 1.37). No patient required further revision. Five patients (18%) complained of hypersensitive scars from the reconstructive surgery that made kneeling difficult. CONCLUSIONS: There were satisfactory results after ACL revision surgery using quadriceps tendon and a 2-incision technique at a minimum 3 years' follow-up; 93% of patients returned to sports activities. LEVEL OF EVIDENCE: Level IV, case series, no control group.