Effect of sequential treatments with alendronate,parathyroid hormone (1–34) and raloxifene on cortical bone mass and strength in ovariectomized rats

Anti-resorptive and anabolic agents are often prescribed for the treatment of osteoporosis continuously or sequentially for many years. However their impact on cortical bone quality and bone strength is not clear.MethodsSix-month old female rats were either sham operated or ovariectomized (OVX). OVX rats were left untreated for two months and then were treated with vehicle (Veh), hPTH (1–34) (PTH), alendronate (Aln), or raloxifene (Ral) sequentially for three month intervals, for a total of three periods. Mid-tibial cortical bone architecture, mass, mineralization, and strength were measured on necropsy samples obtained after each period. Bone indentation properties were measured on proximal femur necropsy samples.ResultsEight or more months of estrogen deficiency in rats resulted in decreased cortical bone area and thickness. Treatment with PTH for 3 months caused the deposition of endocortical lamellar bone that increased cortical bone area, thickness, and strength. These improvements were lost when PTH was withdrawn without followup treatment, but were maintained for the maximum times tested, six months with Ral and three months with Aln. Pre-treatment with anti-resorptives was also somewhat successful in ultimately preserving the additional endocortical lamellar bone formed under PTH treatment. These treatments did not affect bone indentation properties.SummarySequential therapy that involved both PTH and anti-resorptive agents was required to achieve lasting improvements in cortical area, thickness, and strength in OVX rats. Anti-resorptive therapy, either prior to or following PTH, was required to preserve gains attributable to an anabolic agent.     

α-Actinin-3 deficiency is associated with reduced bone mass in human and mouse

Bone mineral density (BMD) is a complex trait that is the single best predictor of the risk of osteoporotic fractures. Candidate gene and genome-wide association studies have identified genetic variations in approximately 30 genetic loci associated with BMD variation in humans. α-Actinin-3 (ACTN3) is highly expressed in fast skeletal muscle fibres. There is a common null-polymorphism R577X in human ACTN3 that results in complete deficiency of the α-actinin-3 protein in approximately 20% of Eurasians. Absence of α-actinin-3 does not cause any disease phenotypes in muscle because of compensation by α-actinin-2. However, α-actinin-3 deficiency has been shown to be detrimental to athletic sprint/power performance. In this report we reveal additional functions for α-actinin-3 in bone. α-Actinin-3 but not α-actinin-2 is expressed in osteoblasts. The Actn3^−/− mouse displays significantly reduced bone mass, with reduced cortical bone volume (− 14%) and trabecular number (− 61%) seen by microCT. Dynamic histomorphometry indicated this was due to a reduction in bone formation. In a cohort of postmenopausal Australian women, ACTN3 577XX genotype was associated with lower BMD in an additive genetic model, with the R577X genotype contributing 1.1% of the variance in BMD. Microarray analysis of cultured osteoprogenitors from Actn3^−/− mice showed alterations in expression of several genes regulating bone mass and osteoblast/osteoclast activity, including Enpp1, Opg and Wnt7b. Our studies suggest that ACTN3 likely contributes to the regulation of bone mass through alterations in bone turnover. Given the high frequency of R577X in the general population, the potential role of ACTN3 R577X as a factor influencing variations in BMD in elderly humans warrants further study.     

Pelvis width associated with bone mass distribution at the proximal femur in children 10–11 years old

Differences in skeletal geometry may generate different patterns of mechanical loading to bone. Impact and muscle loading during physical activity have been shown to influence skeletal geometry. The purpose of this study was to compare geometric measures of the pelvis and proximal femur (PF) of young children and to analyze the contribution and potential interaction of these geometric measures with physical activity on PF bone mass distribution. Participants were 149 girls and 145 boys, aged 10–11 years. Total body and left hip DXA scans were used to derive pelvic and PF geometric measures and PF bone mineral density (BMD) at the femoral neck (FN), trochanter (TR), and intertrochanter (IT). These subregions were used to represent bone mass distribution via three BMD ratios: FN:PF, TR:PF, and IT:PF. Physical activity was objectively measured using accelerometry, and maturity was estimated as the years of distance from peak height velocity. When compared to boys, girls had a wider pelvic diameter and greater interacetabular distances (p < 0.001), lower BMD at FN, TR, and IT (p < 0.05), and higher TR:PF (p < 0.001). After controlling for maturity, body height, and lean body mass, the interacetabular distance in girls explained 21.1 % (β = 0.713, p < 0.001) in TR:PF and 2.9 % (β = ?0.179, p = 0.031) in the IT:PF. Neck–shaft angle explained 5.6 % (β = ?0.265, p = 0.001) of the IT:PF and 3.1 % (β = 0.194, p = 0.018) of the FN:PF. In boys, FN axis length explained 2.9 % (β = 0.195, p = 0.040) of TR:PF. There was no main effect of physical activity or interaction effect with pelvic geometry in explaining BMD differences among the subregions of the PF. Even before sexual dimorphism, girls have a wider pelvis than boys, which accounted for proportionally greater BMD of the TR than other subregions of the PF.     

Are bone turnover markers associated with volumetric bone density,size, and strength in older men and women? The AGES–Reykjavik study

Summary

Association between serum bone formation and resorption markers and bone mineral, structural, and strength variables derived from quantitative computed tomography (QCT) in a population-based cohort of 1745 older adults was assessed. The association was weak for lumbar spine and femoral neck areal and volumetric bone mineral density.

Introduction

The aim of this study was to examine the relationship between levels of bone turnover markers (BTMs; osteocalcin (OC), C-terminal cross-linking telopeptide of type I collagen (CTX), and procollagen type 1N propeptide (P1NP)) and quantitative computed tomography (QCT)-derived bone density, geometry, and strength indices in the lumbar spine and femoral neck (FN).

Methods

A total of 1745 older individuals (773 men and 972 women, aged 66–92 years) from the Age, Gene/Environment Susceptibility (AGES)–Reykjavik cohort were studied. QCT was performed in the lumbar spine and hip to estimate volumetric trabecular, cortical, and integral bone mineral density (BMD), areal BMD, bone geometry, and bone strength indices. Association between BTMs and QCT variables were explored using multivariable linear regression.

Results

Major findings showed that all BMD measures, FN cortical index, and compressive strength had a low negative correlation with the BTM levels in both men and women. Correlations between BTMs and bone size parameters were minimal or not significant. No associations were found between BTMs and vertebral cross-sectional area in women. BTMs alone accounted for only a relatively small percentage of the bone parameter variance (1–10 %).

Conclusion

Serum CTX, OC, and P1NP were weakly correlated with lumbar spine and FN areal and volumetric BMD and strength measures. Most of the bone size indices were not associated with BTMs; thus, the selected bone remodeling markers do not reflect periosteal bone formation. These results confirmed the limited ability of the most sensitive established BTMs to predict bone structural integrity in older adults.

     

Detection of bone and cartilage-related proteins in plasma of patients with a bone fracture using liquid chromatography–mass spectrometry

Following bone fracture, a large number of growth factors, cytokines, and their cognate receptors involved in the repair process are active at the fracture site. To determine whether they appear in patients’ blood as candidate biomarkers for following the outcome of healing, we analysed the plasma of 25 patients with an acute bone fracture following affinity plasma purification, SDS gel electrophoresis and liquid chromatography - tandem mass spectrometry (LC-MS/MS). Two hundred and thirteen nonredundant proteins were identified in the in-gel analysis of pooled plasma proteins. Gene ontology (GO) analysis indicated that a majority of detected proteins were of extracellular origin, whereas only a small number were of intracellular (cytosol and nucleus) origin. A significant proportion of detected proteins was involved in the cell growth and proliferation, transport and coagulation. Twelve proteins were potentially related to bone and cartilage metabolism, and several have not been previously identified in the plasma, including: TGF-β induced protein IG-H₃, cartilage acidic protein 1, procollagen C proteinase enhancer protein and TGF-β receptor III.

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Résumé Après une fracture, un grand nombre de facteurs de croissance, cytokines et leurs récepteurs apparentés interviennent dans le processus de réparation des foyers de fracture. Nous avons analysé ces différents facteurs circulants chez 25 patients ayant présenté une fracture après purification du sang, électrophorèses, chromatographie et spectrographie de masse. 213 protéines ont été identifiées. L’analyse génétique de la majorité de ces protéines montre qu’elles sont d’origine extra cellulaires avec un très petit nombre de protéines intra cellulaires provenant notamment du noyau. Une proportion significative des protéines détectées intervient au niveau de la croissance, de la prolifération cellulaire et des phénomènes de coagulation. 12 protéines sont spécifiquement en rapport avec les métabolismes osseux et cartilagineux, plusieurs d’entre-elles n’avaient pas été préalablement identifiées au niveau du plasma comme la TGF-β, la protéine IG-H3, la CAP 1, le procollagène de type C, le TGF-β récepteur III.

     

On rho, a marrow mediator, and estrogen: Their roles in bone strength and "mass" in human females, osteopenias, and osteoporoses—insights from a new paradigm

From existing evidence, this article argues that six assumptions could explain important estrogen effects on a woman's bone strength and "mass". T_h_e_ e_v_i_d_e_n_c_e_: Strains above a "modeling threshold" cause modeling to increase bone strength and "mass"; under lesser strains, modeling stays OFF. Remodeling by basic multicellular units (BMUs) turns bone over in small "packets," and "rho" signifies any difference in how much bone completed BMUs make and resorb. Where strains exceed a lower "remodeling threshold," rho approaches zero, so that remodeling conserves bone. When strains fall below this threshold, as in acute disuse, rho becomes negative, but only next to marrow, so remodeling removes bone only there. The bone lost during menopause also comes from bone next to marrow, so rho became more negative there too. Simultaneously, and in both cases, bone on periosteal and Haversian surfaces is conserved, meaning rho approaches zero there. T_h_e_ a_s_s_u_m_p_t_i_o_n_s_: (A) Estrogen lowers the threshold for BMU creations on all bone surfaces or envelopes, so loss of the hormone at menopause would increase those creations on all envelopes. (B) Estrogen and acute disuse have no direct effect on rho on any bone envelope. (C) Estrogen and acute disuse do affect some mediator(s) in marrow that can secondarily affect BMUs next to it. (D) That mediator has its own strain threshold, and estrogen lowers it. (E) Loss of estrogen raises that threshold, which causes the mediator to make rho more negative in BMUs next to marrow; that would increase bone loss only there, as would acute disuse, because it would reduce strains below that threshold. (F) Estrogen does not affect the modeling threshold, so it would have no direct effect on cortical bone modeling and outside bone diameter (but by affecting bone length, muscle strength, and physical activities, it might affect modeling indirectly). Those assumptions now have considerable support (although it does not yet amount to proof). The text discusses some of their implications for bone and osteoporosis research. Received: Oct. 1, 1997 / Accepted: Nov. 6, 1997     

Abnormal expression of Col X, PTHrP, TGF-β, bFGF, and VEGF in cartilage with Kashin–Beck disease

The purpose of the current study was to investigate the abnormal expression of Col X, PTHrP, TGF-β, bFGF, and VEGF in cartilage from patients with Kashin–Beck disease (KBD) to understand the pathogenesis of chondronecrosis in KBD. Articular cartilage and growth plate cartilage collected were divided into four groups: control children (8 samples, 5 cases), KBD children (19 samples, 9 cases), control adults (8 samples, 6 cases), and KBD adults (16 samples, 15 cases). The presence of PTHrP, TGF-β₁, bFGF, VEGF, and collagen X in articular cartilage and in growth plate cartilage was analyzed by immunohistochemistry. Articular cartilage and growth plate were each divided in three zones, and the rate of positive cells was counted by light microscope for cytoplasmic and pericellular staining. Results showed that (1) in KBD children, Col X expression was lower in the deep zone of growth plate cartilage than in normal children; in articular cartilage of KBD adults, however, collagen X expression was higher in the middle zone compared to the controls; (2) staining for bFGF, PTHrP, TGF-β₁, and VEGF in KBD adult patients was prominent in the chondrocyte clusters and the eroded surface of articular cartilage, and the percentage of chondrocyte staining was significantly higher than in control samples (t = 3.64–10.34, df = 12 for children and 19 for adults, P = 0.002–0.0001); and (3) the enhanced PTHrP, TGF-β₁, and VEGF staining in the deep and middle zone of KBD articular cartilage correlated with the high incidence of chondronecrosis in the middle zone (48.5% ± 10.2%) and deep zone (70.6% ± 27.0%) of adult KBD cartilage. In conclusion, Col X expression was reduced in areas of chondrocyte necrosis in the deep zone of KBD articular cartilage, indicating changes in terminal chondrocyte differentiation. PTHrP, TGF-β₁, and VEGF expression was significantly altered and indicated degenerative changes in KBD cartilage, which initially resemble those occurring in osteoarthritis, but lead eventually to chondronecrosis, an event not observed in osteoarthritis.     

A case–control study of fractures in men with idiopathic osteoporosis: Fractures are associated with older age and low cortical bone density

ObjectivesTo determine biochemical, radiological and micro-architectural bone factors related to fragility fractures in idiopathic male osteoporosis (IMO) patients. IMO is a rare disorder characterized by low areal bone mineral density (aBMD) (Z-score < ? 2) occurring in men after excluding secondary causes of low BMD.MethodsWe conducted a case–control study in 31 patients with fragility fracture (IMO F +) that had occurred after the age of 40 years and 37 without fracture (IMO F–). We first compared IMO group to 40 age-matched disease-free men. We measured aBMD and bone micro-architectural indices at distal radius and tibia sites with a HR-pQCT scan (XtremeCT) using standard and extended cortical analysis. Urine and blood samples were collected in order to determine the levels of bone-turnover markers and the potential determinant of bone fragility. Models of analysis of covariance, including age, height and weight as adjustment factors, were used to compare the groups.ResultsCompared to their controls, IMO patients showed marked disturbance of their micro‐architectural parameters at tibia and radius affecting both trabecular and cortical parameters. IMO F + subjects were significantly older than IMO F ? subjects (58 ± 8 vs. 53 ± 9 yrs, p = 0.01). BMD Z-score at the total-hip was significantly lower in IMO F + (? 1.3 ± 0.5 vs. ? 0.9 ± 0.8 g/cm², p = 0.01). After adjustment, trabecular micro‐architectural parameters, biochemical markers and hormonal parameters were not different in the 2 groups. At distal tibia, cortical v-BMD was significantly lower in IMO F + patients (799 ± 73 vs. 858 ± 60 mg/cm³, p = 0.03), while cortical thickness was not different.ConclusionOur results show that patients with IMO display a marked disturbance of trabecular and cortical bone micro-architecture, and that age and low cortical density are determinants of the fracture occurrence.     

Parathyroid hormone and large related C-terminal fragments increase at different rates with worsening of renal function in chronic kidney disease patients. A possible indicator of bone turnover status?

BACKGROUND: The intact parathyroid hormone (PTH) serum value has been the non-invasive biomarker of choice for the early diagnosis of renal bone disease in the chronic kidney disease (CKD) patient population. It has now been known that the intact PTH assay value is the sum of 1-84 PTH (true hypercalcemic PTH) and large C-terminal PTH fragments, mainly 7-84 PTH, a fragment with hypocalcemic hormone actions. AIM: The aim of this study was to investigate the differences among the different functional stages of CKD in the following PTH parameters: intact PTH, 1-84 PTH, 7-84 PTH, and the ratio 1-84 PTH/7-84 PTH. GFR (clearance of 99mTc-DTPA) was measured in 164 (85 males and 79 females) adult CKD patients with different degrees of renal function impairment (serum creatinine 0.50 12.1 mg/dl, mean 2.00). PATIENTS AND METHODS: Plasma concentrations of calcium, phosphate, 1-84 PTH and intact PTH were also measured. The value of 7-84 PTH was calculated as the difference between intact PTH and 1-84 PTH. The reduction of, GFR was accompanied by an increase of intact PTH, with a prevalent increase of 7-84 PTH over 1-84 PTH, resulting in a decrease of the ratio 1-84 PTH/7-84 PTH. RESULTS: The values of 7-84 PTH showed a discrimination between Stages 1 and 2 (GFR > 60 ml/min ) and Stage 3 (GFR 30 60 ml/ min) CKD patient populations. In fact, 7-84 PTH was already significantly increased in patients at CKD Stage 3. The analysis of individual patients indicated that a low value (< 1.4) of the ratio 1-84 PTH/7-84 PTH, suggestive for low bone turnover, was already found in more than 20% of CKD Stage 3 patients. CONCLUSION: The results of the present study demonstrate that the reduction in GFR is accompanied by a higher increase in 7-84 PTH with respect to 1-84 PTH, which suggests the possibility that bone metabolism and calcemic status are already reduced in patients with moderate renal failure (CKD Stage 3).     

A specific haplotype in the 3′ end of estrogen-receptor alpha gene is associated with low bone mineral density in premenopausal women and increased risk of postmenopausal osteoporosis

It is well established that the development of postmenopausal osteoporosis is under genetic influence. We have recently identified a synonymous single nucleotide polymorphism (SNP) in exon 8 of estrogen receptor- (ER) gene in the vicinity of the stop codon (G2014A) that is associated with an increased risk of postmenopausal osteoporosis. In the present study, we attempted to locate SNPs in the 3-unstranslated region (3UTR) of the ER gene that are in linkage disequilibrium with the exon 8 SNP and assessed their utilization in the risk assessment of postmenopausal osteoporosis in 352 Thai postmenopausal women. The association with bone mineral density (BMD) in premenopausal women was also investigated in 202 premenopausal women. A C to A SNP 1,748 nucleotides distal to the end of the stop codon (C3768A) was identified. The C3768A SNP was not overrepresented in subjects with osteoporosis. However, the presence of the A-C haplotype allele based on the A2014 and C3768 alleles was significantly related to the risk of osteoporosis independently of age, body weight, the G2014A and C3768A SNPs (odds ratio 2.36, 95% CI 1.42–3.91). Moreover, the presence of the A-C haplotype allele was associated with lower femoral neck BMD in premenopausal women ( P =0.05). We concluded that a specific haplotype in the 3 end of the ER gene is associated with lower BMD in premenopausal women and is associated with a higher risk of osteoporosis in postmenopausal women. It is likely that the haplotype allele exerts its influence on bone as early as during young adulthood to increase the risk of osteoporosis later in life.     

The expression of syndecan-1 and -2 is associated with Gleason score and epithelial-mesenchymal transition markers,E-cadherin and β-catenin,in prostate cancer

The epithelial-mesenchymal transition (EMT) is considered a key step in tumor progression, where the invasive cancer cells change from epithelial to mesenchymal phenotype. During this process, a decrease or loss in adhesion molecules expression and an increase in migration molecules expression are observed. The aim of this work was to determine the expression and cellular distribution of syndecan-1 and -2 (migration molecules) and E-cadherin and β-catenin (adhesion molecules) in different stages of prostate cancer progression. A quantitative immunohistochemical study of these molecules was carried out in tissue samples from benign prostatic hyperplasia and prostate carcinoma, with low and high Gleason score, obtained from biopsies archives of the Clinic Hospital of the University of Chile and Dipreca Hospital. Polyclonal specific antibodies and amplification system of estreptavidin-biotin peroxidase and diaminobenzidine were used. Syndecan-1 was uniformly expressed in basolateral membranes of normal epithelium, changing to a granular cytoplasmatic expression pattern in carcinomas. Syndecan-2 was observed mainly in a cytoplasmatic granular pattern, with high immunostaining intensity in areas of low Gleason score. E-cadherin was detected in basolateral membrane of normal epithelia showing decreased expression in high Gleason score samples. β-Catenin was found in cell membranes of normal epithelia changing its distribution toward the nucleus and cytoplasm in carcinoma samples. We concluded that changes in expression and cell distribution of E-cadherin and β-catenin correlated with the progression degree of prostate adenocarcinoma, suggesting a role of these molecules as markers of progression and prognosis. Furthermore, changes in the pattern expression of syndecan-1 and -2 indicate that both molecules may be involved in the EMT and tumor progression of prostate cancer.     

Nephrocalcinosis and hyperlipidemia in rats fed a cholesterol- and fat-rich diet: association with hyperoxaluria, altered kidney and bone minerals, and renal tissue phospholipid–calcium interaction

To determine whether an “atherogenic” diet (excess of cholesterol and neutral fat) induces pathological calcification in various organs, including the kidney, and abnormal oxalate metabolism, 24 male Sprague-Dawley rats were fed either normal lab chow (controls, n=12) or the cholesterol- and fat-rich experimental diet (CH-F, n=12) for 111 ± 3 days. CH-F rats developed dyslipidemia [high blood levels of triglycerides, total, low-density lipoprotein (LDL)-, very low-density lipoprotein (VLDL)-, high-density lipoprotein (HDL)-bound cholesterol, total phospholipids], elevated serum total alkaline phosphatase and lactate dehydrogenase (LDH) levels, in the absence of changes in overall renal function, extracellular mineral homeostasis [serum protein-corrected total calcium, magnesium, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25(OH)₂D)], plasma glycolate and oxalate levels. There was a redistribution of bone calcium and enhanced exchange of this within the extraosseous space, which was accompanied by significant bone calcium loss, but normal bone histomorphometry. Liver oxalate levels, if expressed per unit of defatted (DF) dry liver, were three times higher than in the controls. Urinary glycolate, oxalate, calcium and total protein excretion levels were elevated, the latter showing an excess of proteins >100 kD and a deficit of proteins >30–50 kD. Urinary calcium oxalate supersaturation was increased, and calcium phosphate supersaturation was unchanged. There were dramatically increased (by number, circumference, and area) renal calcium phosphate calcifications in the cortico-medullary region, but calcium oxalate deposits were not detectable. Electron microscopy (EM) and elemental analysis revealed intratubular calcium phosphate, apparently needle-like hydroxyapatite. Immunohistochemistry of renal tissue calcifications revealed co-localization of phospholipids and calcium phosphate. It is concluded that rats fed the CH-F diet exhibited: (1) a spectrum of metabolic abnormalities, the more prominent being dyslipidemia, hyperoxaluria, hypercalciuria, dysproteinuria, loss of bone calcium, and calcium phosphate nephrocalcinosis (NC); and (2) an interaction between calcium phosphate and phospholipids at the kidney level. The biological significance of these findings for the etiology of idiopathic calcium urolithiasis in humans is uncertain, but the presented animal model may be helpful when designing clinical studies. Received: 12 April 2000 / Accepted: 3 August 2000     

Changes in the contents of enzymatic immature, mature, and non-enzymatic senescent cross-links of collagen after once-weekly treatment with human parathyroid hormone (1�C34) for 18?months contribute to improvement of bone strength in ovariectomized monkeys

Summary  

Improvements in total content of enzymatic cross-linking, the ratio of hydroxylysine-derived enzymatic cross-links, and non-enzymatic advanced glycation end product cross-link formation from once-weekly administration of hPTH(1–34) for 18 months in OVX cynomolgus monkeys contributed to the improvement of bone strength.     

Recurrent vesical calculi, hypercalciuria, and biochemical evidence of increased bone resorption in an adult male with paraplegia due to spinal cord injury: is there a role for intermittent oral disodium etidronate therapy for prevention of calcium phosphate bladder stones?

STUDY DESIGN: Clinical case report with comments by colleagues from Sweden, Poland, Spain, Brazil, Japan, Belgium and Switzerland. OBJECTIVES: To discuss the role of disodium etidronate therapy for prevention of calcium phosphate vesical calculi in persons with spinal cord injury, who have hypercalciuria and biochemical evidence of increased bone resorption. SETTING: Regional Spinal Injuries Centre, Southport, UK. METHODS: A 21-year-old male sustained paraplegia (T-10; ASIA scale: A) in a road traffic accident in June 2001. He had an indwelling urethral catheter until the end of August 2001, when he started self-catheterisation. He developed bladder stones and electrohydraulic lithotripsy (EHL) was performed in May 2002. All stone fragments were removed. Recurrence of vesical calculi was noted in October 2002. These stones were fragmented by lithoclast lithotripsy in two sessions, in December 2002 and February 2003; all stone fragments were removed at the end of the second session. This patient reverted to indwelling catheter drainage when vesical calculi recurred. In September 2003, X-ray of the abdomen showed recurrence of vesical calculi. By February 2004, the stones had increased in size and number. EHL of vesical calculi was again performed in April 2004. Complete clearance was achieved. RESULTS: A 24-h urinalysis detected hypercalciuria--18.7 mmol/day (reference range: 2.5-7.5). Biochemical analysis of vesical calculus revealed calcium phosphate (85%) and magnesium ammonium phosphate (15%). Plasma C-terminal telopeptide (CTX) was increased - 1.06 ng/ml (reference range: 0.1-0.5 ng/ml). Free deoxypyridinoline/creatinine ratio (fDPD/Cr) in urine was also increased - 20.2 (reference range: 2.3-5.4). In April 2004, this patient was prescribed disodium etidronate 400 mg day. Nearly 3 months after commencing therapy with etidronate, plasma CTX decreased to 0.87 ng/ml. fDPD/Cr in urine also decreased to 12.4. After 4 months of etidronate therapy, 24-h urinary calcium excretion had decreased to 6.1 mmol/day. CONCLUSION: Etidronate (400 mg daily) is a very effective inhibitor of calcium phosphate crystallisation. Etidronate decreased urinary excretion of calcium, an important factor in prevention of calcium phosphate bladder stones. Etidronate therapy is not a substitute for other well-established methods for prevention of vesical calculi in spinal cord injury patients, for example, large fluid intake, avoiding long-term catheter drainage. Intermittent therapy with etidronate may be considered in selected patients, in whom hypercalciuria persists after instituting nonpharmacological therapy for an adequate period, for example, early mobilisation, weight-bearing exercises, and functional electrical stimulation. However, possible side effects of etidronate, and the fact that etidronate is not licensed in United Kingdom for prevention of urolithiasis, should be borne in mind.     

The risk of associated urological abnormalities in children with pre and postnatal occasional diagnosis of solitary,small or ectopic kidney: is a complete urological screening always necessary?

OBJECTIVE: Voiding cystourethrogram (VCUG) and radionuclide scan is recommended for patients with solitary (secondary to aplasia or multicystic dysplasia), hypoplasic or single ectopic kidney, to detect associated anomalies (vesicoureteric reflux, obstructive uropathies). With the increase of occasional diagnosis, mainly by fetal ultrasound (US), the possibility of an unjustified extension of diagnostic work up must be prevented. Aim of this paper was to estimate the incidence of associated anomalies in asymptomatic cases without associated US signs of hydronephrosis. MATERIALS AND METHODS: Among 158 Patients examined there were 81 solitary kidneys (26 multicystic dysplasia), 27 small kidneys, 50 single ectopic kidneys); prenatal diagnosis was recorded in 86%. Incidence of associated anomalies was compared with figures resulting when symptomatic cases or with hydronephrosis were excluded. RESULTS: Vesicoureteral reflux or obstruction were found in 17% of solitary kidneys, 70% of hypoplasic kidneys and 2% of single ectopic kidneys. Among those (120 cases) without infection or hydronephrosis, incidence decreased, respectively to 5, 60 and 0%. CONCLUSIONS: Associated anomalies are reported to affect up to 48% of solitary kidneys and about 30% of single ectopic; 80% of severe reflux are usually associated to small kidneys. In our series of solitary and ectopic kidneys incidence of abnormalities was significantly less and fell to negligible values when occasionally detected, undilated cases were considered. On this basis, indiscriminate urological screening simply based on the occasional pre or postnatal detection of undilated solitary or ectopic kidney appears to be unjustified. Small kidneys deserve special attention and VCUG is always indicated.     

Greater intake of fruit and vegetables is associated with a lower risk of osteoporotic hip fractures in elderly Chinese: a 1:1 matched case–control study

Summary

In this case–control study, we examined the relationship between the consumption of fruit and vegetables and risk of hip fractures in 646 pairs of incident cases and controls in elderly Chinese. We found that greater consumption of both fruit and vegetables in men and vegetables in women was associated with a lower risk of osteoporotic hip fractures in elderly Chinese.

Introduction

The association between fruit and vegetable consumption and the risk of osteoporotic fractures remains controversial due to limited published evidence. The purpose of this study was to determine whether consuming fruits and vegetables has a protective effect against hip fractures.

Methods

Between January 2008 and December 2012, 646 (162 males, 484 females) incident cases (70.9?±?6.8 years) of hip fractures were enrolled from five hospitals, with 646 sex- and age-matched (±3 years) controls (70.7?±?6.8 years) from hospitals or the community. Face-to-face interviews were conducted to assess habitual dietary intakes using a 79-item food frequency questionnaire and various covariates by structured questionnaires.

Results

Multivariate conditional logistic regression analyses showed dose-dependent inverse correlations between the intake of total fruit (p-trend?=?0.014), total vegetables (p-trend <0.001), fruits and vegetables combined (p-trend?<?0.001) and the risk of hip fractures after adjustment for sociodemographic characteristics, dietary factors and other potential confounders. The adjusted odds ratios (95 % confidence interval) for hip fractures in the top quartiles (vs. the lowest quartiles) for the intake of fruits, vegetables and the combination of fruits and vegetables were 0.53 (0.32–0.87), 0.37 (0.23–0.60) and 0.25 (0.15–0.41), respectively. Stratified analyses showed that the benefits remained significant in males (p?=?0.001) but not in females (p?=?0.210) (p-interaction 0.045). Among the subcategories of fruits and vegetables, similar associations were observed for all subgroups except light-coloured fruits.

Conclusions

Our findings suggest that greater consumption of both fruits and vegetables in men and vegetables in women may decrease the risk of osteoporotic hip fractures in elderly Chinese.