The Relationship Between Scoliosis, Spinal Bone Density, and Truncal Muscle Strength in Familial Dysautonomia Patients.

This combined retrospective and prospective study aimed to investigate the relationship between scoliosis, spinal bone mineral density (BMD), and truncal muscle strength in patients with familial dysautonomia (FD). A total of 79 FD patients (40 male, 39 female) aged 5-44 years were included. The severity of scoliosis, lumbar spine BMD (Z-score), and truncal muscle strength were assessed. Correlations were analyzed using Pearson's correlation coefficient. Inverse correlations were observed between scoliosis severity and BMD (r = - 0.328, p = 0.001), as indicated by increasingly negative Z-score values with worsening osteoporosis. There were also inverse correlations between scoliosis and truncal muscle strength (r = - 0.595, p < 0.001). The correlation between scoliosis and age was notable up to 22 years (r = 0.421, p = 0.01), but not in the older age group (22-44 years). Our study identified inverse correlations between osteoporosis and scoliosis, as well as between scoliosis and truncal muscle strength, in FD patients. These findings suggest that there may be a relationship between bone density, muscle strength, and the severity of spinal curvature in this population. While our results highlight the potential importance of early diagnosis and management of osteoporosis, and possibly the benefits of physical therapy to strengthen truncal muscles, further research is needed to determine the direct impact of these interventions on preventing the progression of scoliosis and its associated complications in FD patients. A long-term longitudinal study could provide more insights into these relationships and inform treatment strategies for FD patients.

Zoledronic acid sequential to teriparatide may promote greater inhibition of bone resorption than zoledronic acid alone.

Background: Teriparatide (TPTD) should be followed by an antiresorptive to maximize bone mineral density gain and anti-fracture protection. Infrequent zoledronic acid (ZOL) administration has demonstrated effectiveness. The duration of ZOL effect following TPTD is unknown. Objective: To evaluate the effect of ZOL on bone resorption marker in a post-TPTD versus ZOL-alone scenario in osteoporotic patients. Design: Retrospective cohort study. Methods: Patients treated with TPTD followed by ZOL (TPTD-ZOL) or with a single ZOL infusion were identified in the database of a tertiary referral center. Clinical and laboratory data, including C-terminal telopeptide of type I collagen (CTX) following ZOL treatment, were compared. Results: Twenty-six patients (93% women) treated with TPTD-ZOL and 41 with ZOL were comparable in age (median 70.1 versus 69.6 years, p = 0.6) and sex. Timing of CTX measurement post-ZOL was the same, median 1.0 year. CTX was lower following TPTD-ZOL (median 142.1 versus 184.2 pg/mL, p = 0.005). In a multivariable regression model (controlled for baseline characteristics), pretreatment with TPTD strongly predicted CTX <150 pg/mL, 1 year following ZOL (odds ratio = 7.5, 95% CI 1.3-58.1, p = 0.03). In a subgroup with sequential CTX measurements following one ZOL, significantly lower levels persisted in the TPTD-ZOL group for a median of 4.4 years follow-up. Conclusion: ZOL-administered sequential to TPTD yielded deeper and more prolonged bone resorption suppression than ZOL alone. Prospective data are needed to confirm whether in a sequential treatment scenario, subsequent ZOL dosing interval should be less frequent.

Romosozumab improves lumbar spine bone mass and bone strength parameters relative to alendronate in postmenopausal women: results from the Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) trial.

The Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) trial (NCT01631214; https://clinicaltrials.gov/ct2/show/NCT01631214) showed that romosozumab for 1 year followed by alendronate led to larger areal bone mineral density (aBMD) gains and superior fracture risk reduction versus alendronate alone. aBMD correlates with bone strength but does not capture all determinants of bone strength that might be differentially affected by various osteoporosis therapeutic agents. We therefore used quantitative computed tomography (QCT) and finite element analysis (FEA) to assess changes in lumbar spine volumetric bone mineral density (vBMD), bone volume, bone mineral content (BMC), and bone strength with romosozumab versus alendronate in a subset of ARCH patients. In ARCH, 4093 postmenopausal women with severe osteoporosis received monthly romosozumab 210 mg sc or weekly oral alendronate 70 mg for 12 months, followed by open-label weekly oral alendronate 70 mg for ≥12 months. Of these, 90 (49 romosozumab, 41 alendronate) enrolled in the QCT/FEA imaging substudy. QCT scans at baseline and at months 6, 12, and 24 were assessed to determine changes in integral (total), cortical, and trabecular lumbar spine vBMD and corresponding bone strength by FEA. Additional outcomes assessed include changes in aBMD, bone volume, and BMC. Romosozumab caused greater gains in lumbar spine integral, cortical, and trabecular vBMD and BMC than alendronate at months 6 and 12, with the greater gains maintained upon transition to alendronate through month 24. These improvements were accompanied by significantly greater increases in FEA bone strength (p < 0.001 at all time points). Most newly formed bone was accrued in the cortical compartment, with romosozumab showing larger absolute BMC gains than alendronate (p < 0.001 at all time points). In conclusion, romosozumab significantly improved bone mass and bone strength parameters at the lumbar spine compared with alendronate. These results are consistent with greater vertebral fracture risk reduction observed with romosozumab versus alendronate in ARCH and provide insights into structural determinants of this differential treatment effect. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Opportunistic screening for osteoporosis and osteopenia by routine computed tomography scan: A heterogeneous, multiethnic, middle-eastern population validation study.

PURPOSE: We aimed define thresholds for HU values observed on opportunistic CT scans that suggest abnormal bone mineral density (BMD) in a heterogeneous Middle Eastern population. METHODS: Consecutive patients who had undergone CT and dual-energy X-ray absorptiometry (DXA) test of the lumbar spine within 6 months were included in this retrospective study. Hounsfield units (HU) on lateral lumbar spine CT and BMD at the spine and hip on DXA were compared. Potential HU thresholds suggestive of abnormal BMD were established using receiver operating characteristic (ROC) analysis. RESULTS: 246 patients (mean age of 64 ±â€¯11.6 years; 83 % female) were included. On DXA, 27 % had osteoporosis, 56 % had osteopenia, and 17 % had normal BMD. To distinguish osteoporosis from non-osteoporosis (osteopenia, normal BMD), a threshold of HU160 had sensitivity 95 % and the balanced threshold was HU121 (sensitivity 74 %, specificity 61 %). To distinguish normal from abnormal BMD (osteoporosis, osteopenia), a threshold of HU110 had specificity 93 % and the balanced threshold was HU149 (sensitivity 76 %, specificity 74 %). CONCLUSIONS: In a heterogeneous Middle-Eastern population, our study supports the reported correlation between HU values on lumbar spine CT and BMD on DXA. In this population, HU > 160 correlates with low probability of osteoporosis on DXA, and screening examination is not warranted unless a vertebral fracture is detected; for HU ≤ 110 there is high probability of abnormal (osteoporosis or osteopenia) BMD, DXA examination is warranted; Finally, for HU 110-160, there is an intermediate chance of abnormal BMD, DXA examination may be warranted in specific patients with other risk factors.

Dissemination of NDM-1 carbapenemase-producer Providencia stuartii strains in Romanian hospitals: a multicentre study.

Several Romanian hospitals have noted increasing isolation of Providencia stuartii strains in recent years, with an alarming rate of carbapenem resistance. In order to provide molecular epidemiological data regarding their dissemination, 77 P. stuartii strains collected from five hospitals located in different regions of Romania were analysed. All strains harboured IncA/C plasmid, and 67 carried the blaNDM-1 gene. Six clonal clusters were differentiated by pulsed-field gel electrophoresis. The predominant subtype was found in all five hospitals. Our study highlights the need for efficient infection-control measures, the optimization of antibiotic use and the targeted surveillance for carbapenemase-producing P. stuartii.

Evidence for Bicarbonate Secretion by Ameloblasts in a Novel Cellular Model.

Formation and growth of hydroxyapatite crystals during amelogenesis generate a large number of protons that must be neutralized, presumably by HCO3 (-)ions transported from ameloblasts into the developing enamel matrix. Ameloblasts express a number of transporters and channels known to be involved in HCO3 (-)transport in other epithelia. However, to date, there is no functional evidence for HCO3 (-)transport in these cells. To address questions related to HCO3 (-)export from ameloblasts, we have developed a polarized 2-dimensional culture system for HAT-7 cells, a rat cell line of ameloblast origin. HAT-7 cells were seeded onto Transwell permeable filters. Transepithelial resistance was measured as a function of time, and the expression of transporters and tight junction proteins was investigated by conventional and quantitative reverse transcription polymerase chain reaction. Intracellular pH regulation and HCO3 (-)transport were assessed by microfluorometry. HAT-7 cells formed epithelial layers with measureable transepithelial resistance on Transwell permeable supports and expressed claudin-1, claudin-4, and claudin-8-key proteins for tight junction formation. Transport proteins previously described in maturation ameloblasts were also present in HAT-7 cells. Microfluorometry showed that the HAT-7 cells were polarized with a high apical membrane CO2 permeability and vigorous basolateral HCO3 (-)uptake, which was sensitive to Na(+)withdrawal, to the carbonic anhydrase inhibitor acetazolamide and to H2DIDS inhibition. Measurements of transepithelial HCO3 (-)transport showed a marked increase in response to Ca(2+)- and cAMP-mobilizing stimuli. Collectively, 2-dimensional HAT-7 cell cultures on permeable supports 1) form tight junctions, 2) express typical tight junction proteins and electrolyte transporters, 3) are functionally polarized, and 4) can accumulate HCO3 (-)ions from the basolateral side and secrete them at the apical membrane. These studies provide evidence for a regulated, vectorial, basolateral-to-apical bicarbonate transport in polarized HAT-7 cells. We therefore propose that the HAT-7 cell line is a useful functional model for studying electrolyte transport by ameloblasts.

Immunomodulatory and potential therapeutic role of mesenchymal stem cells in periodontitis.

Periodontitis is a chronic inflammatory disease leading to alveolar bone destruction, and eventually tooth loss. In genetically or environmentally predisposed individuals periodontopathogenic bacteria trigger an inflammatory immune response where activated macrophages secrete inflammatory cytokines and T helper 17 cells produce interleukin-17, receptor activator of nuclear factor kappa B ligand (RANKL) and tumor necrosis factor-α. Inflammation and the production of RANKL, the key cytokine responsible for osteoclast activation, cause excessive activation of osteoclasts. This results in a decoupling between bone formation and resorption, leading to bone loss. As conventional treatment does not target the inflammatory response and osteoclast activation, its effectiveness is limited. Novel treatments are thus required if we are to cure this disease. Mesenchymal stem cells (MSCs), including those of dental origin, are potent immunomodulators and are known to be suitable for tissue regeneration. MSCs can inhibit the immune response by suppressing T cells, inducing regulatory T cells and converting dendritic cells and macrophages into a regulatory phenotype. Additionally, genetic modulation may enhance the therapeutic potential of MSCs. In the present review the authors describe the potential use of MSCs, either unmodified or engineered for therapeutic purposes in periodontitis, with special emphasis on MSCs from dental pulp and periodontal ligament. The paper envisions that multiple targeting of this inflammatory disease by modulating the immune response, promoting bone regeneration and inhibiting bone resorption might yield significantly improved treatment outcomes when combined with conventional treatment modalities.

2013 International Society for Clinical Densitometry Position Development Conference: Task Force on Normative Databases.

Following the standard protocol for development of Official Positions for the International Society for Clinical Densitometry, the Expert Panel heard the report and recommendations from the Task Force on Normative Databases; using the RAND methodology, agreement was reached on the following statements: 1. Manufacturers should continue to use their own databases for the lumbar spine as the reference standard for T-scores. 2. Manufacturers should continue to use National Health and Nutrition Examination Survey III data as the reference standard for femoral neck and total hip T-scores. 3. If local reference data are available, they should be used to calculate only Z-scores but not T-scores. 4. A uniform Caucasian (non-race adjusted) female reference database should be used to calculate T-scores for men of all ethnic groups.

Osteoporosis in young adults: pathophysiology, diagnosis, and management.

Postmenopausal osteoporosis is mainly caused by increased bone remodeling resulting from estrogen deficiency. Indications for treatment are based on low areal bone mineral density (aBMD, T-score ≤ -2.5), typical fragility fractures (spine or hip), and more recently, an elevated 10-year fracture probability (by FRAX®). In contrast, there is no clear definition of osteoporosis nor intervention thresholds in younger individuals. Low aBMD in a young adult may reflect a physiologically low peak bone mass, such as in lean but otherwise healthy persons, whereas fractures commonly occur with high-impact trauma, i.e., without bone fragility. Furthermore, low aBMD associated with vitamin D deficiency may be highly prevalent in some regions of the world. Nevertheless, true osteoporosis in the young can occur, which we define as a T-score below -2.5 at spine or hip in association with a chronic disease known to affect bone metabolism. In the absence of secondary causes, the presence of fragility fractures, such as in vertebrae, may point towards genetic or idiopathic osteoporosis. In turn, treatment of the underlying condition may improve bone mass as well. In rare cases, a bone-specific treatment may be indicated, although evidence is scarce for a true benefit on fracture risk. The International Osteoporosis Foundation (IOF) convened a working group to review pathophysiology, diagnosis, and management of osteoporosis in the young, excluding children and adolescents, and provide a screening strategy including laboratory exams for a systematic approach of this condition.

The outcome of surgically treated femur fractures associated with long-term bisphosphonate use.

INTRODUCTION: Bisphosphonates (BPs) evolved as the mainstay for the treatment of osteoporosis, reducing the incidence of fractures. Recently several publications described the occurrence of low-energy subtrochanteric and femoral shaft fractures associated with long-term BP use. The aim of this study was to describe the outcome of surgically treated femur fractures associated with prolonged BP use. PATIENTS: Fifteen patients suffering from 17 atypical femoral fragility fractures associated with long-term (>3 years) BP use were located. Data included fracture type, time of BP use, last bone mineral density DEXA scores for the femoral neck and spine, type of surgery, and the need for revision. RESULTS: Fourteen female patients and one male patient were identified. The median age was 73 years (range, 51-80 years). The mean BP use was 7.8 years (range, 4-13 years). Fourteen patients had low-energy traumatic femoral shaft (proximal and distal) or low subtrochanteric fractures. The mean lumbar spine (for 13 patients) bone mineral density T-score was -3.0, whereas mean femoral neck T-score was -1.8 with only three patients in the osteoporotic range.Fracture healing after the first procedure for patients treated with nails was 54%, with 46% of patients requiring revision surgery. These included nail dynamization, exchange nailing, and one revision to a blade plate. All of these eventually healed. CONCLUSIONS: BP-related fractures are a recently described phenomenon. Despite initial osteoporosis, the DEXA scan may appear outside the osteoporotic range for the femoral neck in these patients. In addition, a much higher failure rate with intramedullary nailing requiring revision surgery may occur with these patients.

Significant and continuous improvement in bone mineral density among type 1 Gaucher disease patients treated with velaglucerase alfa: 69-month experience, including dose reduction.

Since bone pathology is a major concern in type 1 Gaucher disease (GD1), we evaluated bone mineral density (BMD) in adults receiving velaglucerase alfa in the seminal Phase I/II and extension trial. Ten treatment-naïve symptomatic patients with GD1 (four men, six women; median age 35years, range 18-62years) were included; of these, four patients were receiving bisphosphonates at enrollment. Using WHO criteria to classify the lumbar spine (LS) and femoral neck (FN) BMD T-scores, respectively, one (10%) and four (40%) patients had osteoporosis; eight (80%) and five (50%) had osteopenia; and one each (10%) was in the normal range, at baseline. By Month 69, two LS and one FN osteopenic patients normalized and one FN osteoporotic patient became osteopenic; change was seen only in patients not receiving bisphosphonates. Significant improvements in BMD Z-scores were seen at the LS by Month 24 and at the FN by Month 33 and were continuous thereafter. In linear mixed models, Z-scores were significantly lower than the reference population at baseline and improved significantly with treatment (LS and FN both P<0.01); analysis of the subgroup of patients not receiving bisphosphonates showed similar results. In conclusion, in this small cohort, velaglucerase alfa was associated with clinically meaningful and statistically significant LS and FN BMD improvements as early as Month 24 (LS) and 33 (FN), despite dose reduction and significant baseline skeletal pathology. These results suggest that velaglucerase alfa may hold promise in the management of skeletal pathology associated with GD1.

Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards.

UNLABELLED: The International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommend that a marker of bone formation (serum procollagen type I N propeptide, s-PINP) and a marker of bone resorption (serum C-terminal telopeptide of type I collagen, s-CTX) are used as reference analytes for bone turnover markers in clinical studies. INTRODUCTION: Bone turnover markers (BTM) predict fracture risk, and treatment-induced changes in specific markers account for a substantial proportion of fracture risk reduction. The aims of this report were to determine their clinical potential in the prediction of fracture risk and for monitoring the treatment of osteoporosis and to set an appropriate research agenda. METHODS: Evidence from prospective studies was gathered through literature review of the PUBMED database between the years 2000 and 2010 and the systematic review of the Agency for Healthcare Research and Quality up to 2001. RESULTS: High levels of BTMs may predict fracture risk independently from bone mineral density in postmenopausal women. They have been used for this purpose in clinical practice for many years, but there is still a need for stronger evidence on which to base practice. BTMs provide pharmacodynamic information on the response to osteoporosis treatment, and as a result, they are widely used for monitoring treatment in the individual. However, their clinical value for monitoring is limited by inadequate appreciation of the sources of variability, by limited data for comparison of treatments using the same BTM and by inadequate quality control. IOF/IFCC recommend one bone formation marker (s-PINP) and one bone resorption marker (s-CTX) to be used as reference markers and measured by standardised assays in observational and intervention studies in order to compare the performance of alternatives and to enlarge the international experience of the application of markers to clinical medicine. CONCLUSION: BTM hold promise in fracture risk prediction and for monitoring treatment. Uncertainties over their clinical use can be in part resolved by adopting international reference standards.

Equipment modification is associated with fewer stress fractures in female Israel border police recruits.

PURPOSE: The study was planned to assess whether combat equipment weight reduction would lead to a reduction in the incidence of stress fractures in female border police infantry recruits taking a 4-month course of basic combat training. METHOD: 213 female border police recruits, 18-19 years of age, undergoing 16 weeks of basic combat training with lighter rifle and lighter closely fitted combat vest, (total 9.4 kg) were followed prospectively for stress fracture (SFx) incidence, compared to a historical control group of 1,210 recruits who trained with traditional equipment (12.5 kg). RESULTS: Equipment modification was associated with a significant reduction in SFx from 18.3% in the control group to 8.0% in the intervention group (p < 0.0001). CONCLUSIONS: This study implies that equipment weight reduction may achieve a significant effect in SFx reduction, Approximating fighting gear to body center of gravity may enhance this effect.

Vectorial bicarbonate transport by Par-C10 salivary cells.

Salivary glands produce a HCO(3)(-)-rich fluid that is important for the neutral milieu in the upper gastrointestinal tract. The molecular mechanism of this secretion is poorly understood. Par-C10, an immortalized rat parotid acinar line, has been shown to secrete Cl(-)- in response to Ca(2+-)-mobilizing stimuli. Our aim was to assess the capacity of polarized monolayers of Par-C10 cells to transport and secrete HCO(3)(-)-. Transepithelial electrolyte movement was evaluated by short-circuit current measurements. Intracellular pH (pH(i)) was measured by microfluorometry in cells loaded with BCECF. Monolayers of Par-C10 cells, grown on Transwell membranes, developed high transepithelial resistance and exhibited vectorial anion secretion which was activated by both ATP and forskolin. The currents were partially inhibited by bumetanide and by withdrawal of HCO(3)(-) indicating the dependence of ion movements on NKCC and on HCO(3)(-) ions, respectively. In HCO(3)(-)-free solutions the recovery of pH(i) from acid loading was abolished by EIPA. In the presence of HCO(3)(-) there was a strong EIPA-insensitive recovery from acid loading which was inhibited by H(2)DIDS. ATP and forskolin stimulated HCO(3)(-) efflux from the cells. Furthermore, HCl(-) withdrawal experiments showed the presence of DNDS-sensitive basolateral anion exchange. In conclusion Par-C10 cells achieve transepithelial transport that is sensitive to both intracellular Ca(2+)- and cAMP-dependent stimulation. We identified Na(+)/H(+) exchange, Na(+)-HCO(3)(-) cotransport and anion exchange at the basolateral side of the cells as being involved in intracellular pH regulation and vectorial HCO(3)(-) secretion. This cell line offers a good model for further studies to understand the molecular mechanisms of salivary HCO(3)(-) secretion.

Molecular aspects of osteopathy in type 1 Gaucher disease: correlation between genetics and bone density.

Bone-related complications in Gaucher disease are considered to be poorly responsive to specific enzyme replacement therapy. Polymorphisms of candidate genes associated with low bone density were investigated to see whether they are correlated with bone mineral density (BMD) and bone involvement in Gaucher disease. Genotyping for polymorphisms in candidate genes (interleukins 1alpha and 1beta, interleukin-1 receptor antagonist; cytochrome P450; collagen 1A1; low-density Lipoprotein Receptor; bone morphogenic protein 4; vitamin D receptor; and estrogen receptor 2beta) were performed using standard methodologies. BMD was measured by dual energy X-ray absorptiometry (DXA). One hundred and ninety-four patients and 100 controls were genotyped for the above polymorphisms. Thirteen haplotypes were obtained, with several correlations with BMD in patients; also, a haplotype (T889-T3954-C511-240VNTR of IL1) was significantly correlated with T-scores and Z-score for femur neck and lumbar spine (p = 0.01) in patients. Haplotypes of bone-specific candidate genes associated with BMD may predict severity of these features in Gaucher disease.

Effects of estradiol and raloxifene on arterial thrombosis in ovariectomized mice.

OBJECTIVE: The effects of estrogen and selective estrogen receptor modulators (eg, raloxifene) on arterial thrombosis are not well defined. This study assessed the manner and mechanism by which estrogen and raloxifene affect homeostatic pathways in ovariectomized mice after acute arterial injury. DESIGN: Female mice (3 weeks old) underwent ovariectomy or sham operation. Five days after surgery, mice were assigned to treatment with estradiol (5.3 nmol/kg), raloxifene (2.7 micromol/kg), or placebo (n = 10-12/group). The biological effects of both treatments were assessed by measurements of bone mass and the degree of uterine atrophy. After 4 months of therapy, carotid artery thrombosis was induced by photochemical injury, and the time to vascular occlusion was measured. RESULTS: Both treatments increased bone mineral density (4.1%-7.85%). Reversal of macroscopic uterine atrophy was observed only in estrogen-treated mice. Ovariectomized mice had a shorter time to occlusion compared with sham-operated mice (70.8 +/- 7.4 vs 103 +/- 11.3 min), suggesting accelerated thrombosis. Both estradiol and raloxifene significantly inhibited intra-arterial thrombosis in ovariectomized mice, prolonging the time to occlusion to 136.33 +/- 13.5 and 141.43 +/- 9.26 min, respectively. Cyclooxygenase-2 levels in the lung tissue were significantly increased by both raloxifene and estradiol with endothelial nitric oxide synthase expression being unaltered. Platelet adhesion (measured by surface coverage under a shear rate of 1,800 s for 2 min) was significantly reduced in ovariectomized animals, being 4.63% +/- 1.47%, 5.78% +/- 1.58%, and 10.04% +/- 1.33% for raloxifene, estradiol, and placebo, respectively. CONCLUSIONS: Ovariectomy amplifies thrombosis. We found that 4 months of treatment with both estradiol and raloxifene attenuates intravascular thrombosis. The antithrombotic effect was accompanied by increased expression of cyclooxygenase-2 and suppression of platelet surface adhesion.

High prevalence of iron deficiency and anemia in female military recruits.

Iron deficiency anemia has long been known to impair physical and mental performance. Iron deficiency itself, even without anemia, may also cause such an effect. Similar to female athletes, women in active military units may have increased risks for iron deficiency and its detrimental effects. Female recruits were screened for anemia and iron store status, and a questionnaire on lifestyle habits and menstruation was completed. Iron depletion (serum ferritin level of <20 microg/L) was found for 77% of study participants. Iron deficiency (ferritin level of <12 microg/L and transferrin saturation of <15%) was found for 15% of study participants. Anemia was found for 24% of subjects, and iron deficiency anemia was found for 10% of subjects. High prevalence of iron depletion, iron deficiency, anemia, and iron deficiency anemia was found among female recruits intended for active military duty. Therefore, a recommendation can be made to screen such female recruits for anemia and iron stores.

Serum levels of osteoprotegerin and osteoprotegerin polymorphisms in Gaucher disease.

Bone involvement in Gaucher disease causes disability and reduced quality of life; loss of function and pain are important indications for enzyme replacement therapy. The purpose of this study was to ascertain whether osteoprotegerin (OPG), which decreases osteoclast activity, is indicative of incipient bone involvement by comparing OPG serum levels to Gaucher disease severity (SSI) and bone mineral density (BMD), and to correlate bone and disease markers to OPG polymorphisms: OPG1-2(A163G), OPG3-4(T129C) and OPG5-6(C1217T). Of 554 patients, 173 Ashkenazi Jewish patients with non-neuronopathic Gaucher disease were enrolled and 32 healthy Ashkenazi Jews served as controls. Serum OPG levels were detected by enzyme-linked immunosorbent assay and BMD was obtained by dual X-ray absorptiometry. OPG polymorphisms were determined in 63 randomly chosen patients. Serum OPG values for patients were not greater than in controls, but showed a statistically significant trend to increase with age (P = 0.057). No correlation existed between OPG levels and BMD or with genotype or other disease markers. A significant correlation was noted between OPG5-6 genotype and SSI. A significant difference was found between the allele distributions of each OPG polymorphism when compared with Caucasians and Ashkenazi Jews. OPG levels probably do not predict BMD in Gaucher disease and hence are not indicative of osteoporosis in Gaucher disease.

Ultrasound-modulated light tomography assessment of osteoporosis.

We present a preliminary series of clinical experiments showing that ultrasound modulation of light in tissues allows tissue properties to be determined well inside the tissue. In this series of clinical experiments the optical scattering coefficient determined by the optical technique is compared with the bone density obtained by dual x-ray absorption. A correlation of 0.84 (p = 0.005) was found for a limited number of patients, showing the potential of this technique for the assessment of osteoporosis.

Treatment preference and tolerability with alendronate once weekly over a 3-month period: an Israeli multi-center study.

BACKGROUND AND AIMS: Osteoporosis is a chronic condition requiring long-term treatment, for which compliance is not easy to achieve. 70 mg of alendronate once weekly (alendronate OW) provides equivalent efficacy to treatment with 10 mg of alendronate once a day (alendronate OD); however, there are relatively few data regarding patient and physician preferences for once-weekly vs daily dosing. The aim of this study was to measure compliance, convenience, tolerance and relative preference of alendronate OW treatment among post-menopausal women with osteoporosis and physician satisfaction, compared with previous treatment with alendronate OD. METHODS: This open-label, prospective multi-center trial was conducted at 14 hospitals and 150 primary-care community clinics in Israel. Post-menopausal osteoporotic women (n = 3710), who had been treated for at least 1 month with alendronate OD during the preceding year, were treated with alendronate OW for 12 weeks. Convenience, satisfaction, tolerance and relative preference of alendronate OW during the trial, compared with past experience with alendronate OD, were recorded. RESULTS: Overall, 96% of the patients preferred the alendronate OW regimen to the 10-mg daily dosage. Nearly all (98%) the patients who completed 12 weeks of treatment, including 77% of patients who had previously discontinued daily treatment due to intolerance, were willing to continue the alendronate OW regimen. Patient-reported compliance with dosing instructions was over 98%. Alendronate OW was well tolerated; only 2.8% of patients discontinued, due to adverse events. Physicians were highly satisfied with the once-weekly dosing regimen, and recommended continued treatment with alendronate OW for 99% of the patients. CONCLUSIONS: The majority of post-menopausal women with osteoporosis, including those who were previously intolerant to alendronate OD, preferred alendronate OW to the once-daily dosing regimen. It is important to consider patient preference when selecting the appropriate treatment for osteoporosis.