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Trabecular bone score (TBS) is an emerging technology that provides information regarding bone microarchitecture. A recent study showed that in healthy girls normal TBS (≥1.35) was achieved within the first year post-menarche. The aims of our study was to assess TBS in adolescents with anorexia nervosa (AN) and to evaluate correlations with clinical, laboratory and densitometric variables.A cohort study of 208 adolescent females (mean age 15.6 ± 1.8 y) hospitalized because of AN between 2003 and 2017 was retrospectively assessed. Demographic and clinical data, including age, weight, height, body mass index (BMI), laboratory parameters and bone mineral density (BMD) measurements by dual-energy X-ray absorptiometry (DXA) were retrieved from the medical charts. Bone mineral apparent density (BMAD) was calculated for each participant. TBS was assessed by reanalyzing DXA spinal images.Mean TBS was 1.308 ± 0.083, lower than the values previously described in healthy adolescents (p 0.001). Compromised microarchitecture was found in 17 participants (8.2%) and partially compromised in 123 (59.1%). TBS was significantly correlated with age, weight standard deviation score (SDS), BMI SDS, BMD measurements of the lumbar spine and total body, BMAD, BMAD Z-score, luteinizing hormone (LH) and 17b-estradiol (E2) level, and was negatively correlated with cortisol (p = 0.017). Participants with regular menstruation or secondary amenorrhea had higher TBS than participants who were pre-menarche or with primary amenorrhea (p 0.001). A stepwise linear regression analysis identified BMD L1-4 Z-score and log E2 as independent predictors of TBS.TBS of adolescent females with AN was found to be lower than TBS of healthy adolescents. Prospective longitudinal studies should be undertaken to investigate whether recovery may result in correction of bone microarchitecture.

Objective: To describe the clinical features of patients with bisphosphonate related ocular side effects (BROSE).Methods: The medical records of all patients with BROSE between January 2009 and December 2019 were reviewed.Results: Nine cases with BROSE were identified. All subjects were female. Median age at diagnosis was of 69 years. The leading indication for bisphosphonate treatment was osteoporosis (n=7), Paget's disease of bone (n=1) and breast cancer (n=1). Six (66.67%) patients presented with uveitis, one (11%) episcleritis and two (22%) with orbital inflammation. Five events (55.5%) occurred within 10 days of initiating the bisphosphonate and the rest (44.44%) developed within 2 weeks to 3 years later. Four (44.44%) patients had concurrent thyroid disease. An association was found between underlying thyroid disease or autoimmunity.Conclusion: BROSE is an uncommon complication of bisphosphonate therapy occurring more frequently in patients with an autoimmune predisposition.

Osteoporosis and its related fractures are major public health concerns. Physical activity (PA) is crucial for bone density preservation and fractures prevention. Yet, gaps in understanding exist regarding how ethno-cultural backgrounds might shape attitudes, intentions and actual PA participation. Based on the theory of planned behaviour (TPB) for predicting PA, the aims of this study were: (i) to compare attitudes, subjective norms, perceived control, intentions and knowledge, across four ethno-cultural groups; (ii) to evaluate the fit of the model we constructed across four ethno-cultural groups of women: Israeli-born Jews and Israeli-born Bedouin-Muslims, immigrants from the Former Soviet Union (FSU) and Ethiopian immigrants. Four hundred women (one hundred from each group), aged >65, completed valid and reliable questionnaires assessing knowledge, TPB components and actual PA. The level of knowledge on osteoporosis was relatively low among all four ethno-cultural groups. Intention to participate in PA was the only variable that directly predicted actual PA. Intention to participate in PA served as a mediator among attitudes, subjective norms, perceived control and actual PA. The structural equation models (SEMs) revealed that among Israeli-born Jews and Ethiopian immigrants, TPB components mediated the link between knowledge and intention to participate in PA. Among FSU immigrants and Israeli Bedouin-Muslims, the knowledge variable was not included in the final model, as its contribution was not significant. It is essential to better understand and augment interventions that enhance PA in the community, and to address the unique needs of each ethno-cultural group.

Recent studies demonstrated an association between low serum sodium levels and reduced bone density. Patients with anorexia nervosa (AN) are at greater risk for osteoporosis as well as for hyponatremia. The aim of the present study was to assess the association between hyponatremia and bone mineral density (BMD) in a large cohort of adolescent inpatients with AN.A historic cohort study of 174 adolescent females (mean age 15.7 ± 1.8 y) hospitalized because of AN between 2003 and 2013. Demographic and clinical data, including age, psychiatric comorbidity, anthropometric measurements, laboratory tests, and BMD scores were obtained from the patients' medical charts.Mean lumbar spine BMD z-score of the patients was lower than expected in the normal population (mean -1.5 ± 1.2) and positively correlated with body mass index standard deviation score (r = 0.42, P 0.0001). Sixty-four participants (36.8%) had at least one episode of hyponatremia during the year preceding the BMD measurement. These participants had a significantly lower lumbar spine BMD z-score (-1.8 ± 1.2 versus -1.3 ± 1.2, P = 0.01) compared with participants with no hyponatremia. Lumbar spine BMD z-score was also positively correlated with the levels of free triiodothyronine (r = 0.16, P = 0.038), 17 b-estradiol (r = 0.23, P = 0.005), and luteinizing hormone (r = 0.25, P = 0.001), and negatively correlated with cortisol levels (r = 0.33, P 0.0001). Having at least one episode of hyponatremia, BMI z-score and cortisol levels were identified as independent predictors of BMD z-score (P 0.001, P 0.001, and P = 0.034, respectively).Hyponatremia may be associated with decreased bone density in adolescent females with AN. Additional studies are required to evaluate whether the correction of hyponatremia will improve BMD.

Bone mineral density (BMD) screening is one of the main means to detect and treat osteoporosis. Yet, the manner in which ethno-cultural background is associated with BMD health cognitions and screening behavior remains limited. Several ethno-cultural groups (n = 100 in each group)&mdash, Israeli-born Jews, Israeli-born Bedouin-Muslims, and Jewish immigrants from the Former Soviet Union (FSU), mean age 70 (SD = 7.1)&mdash, participated in face-to-face interviews in a cross-sectional survey, using valid and reliable questionnaires on BMD screening behavior, knowledge about osteoporosis, and theory of planned behavior (TPB) components. FSU immigrants reported the lowest BMD screening behavior. The multivariate analysis showed that higher knowledge level, positive attitudes, supportive subjective norms, and greater intentions increase the probability of BMD screening behavior. The TPB attitude component had a more pronounced effect on the probability of undergoing BMD screening among Israeli-born Bedouin-Muslims compared to Israeli-born Jews. Our findings contribute to the TPB by deepening our understanding of the associations between TPB components and BMD screening behaviors, from an ethno-cultural perspective. To assure sufficient BMD screening behavior among all ethno-cultural groups, intervention programs&mdash, suited to address the unique characteristics of each ethno-cultural group&mdash, are required.

Denosumab (DMAB) efficacy for treatment of osteoporosis was demonstrated in a pivotal trial with a reduction in vertebral and hip fractures during 3 years, and fracture risk reduction was sustained up to 10 years in an extension study. DMAB causes potent yet reversible inhibition of bone resorption. Bone density declines rapidly upon discontinuation and bone turnover markers increase above baseline in a rebound fashion. Spontaneous multiple vertebral fractures after DMAB discontinuation were recently reported. Prior treatment with bisphosphonates (BP) was postulated to decrease the risk for this alarming phenomenon. We aimed to describe our experience of fractures following DMAB withdrawal with special attention to past history of osteoporosis treatment. A phone survey of physicians engaged in bone metabolism from nine hospitals in Israel was performed. Clinical data of the patients presenting with vertebral fractures upon DMAB discontinuation were summarized and compared to the previously published cases. Nine elderly (74.2 ± 5.3 years) female patients were identified. Most patients had a prolonged prior exposure to BP (7.4 ± 3.2 years). All but one sustained osteoporotic fractures prior to DMAB initiation and their FRAX scores were high. Thirty-six vertebral fractures were identified in nine patients. Eight patients presented with multiple fractures, and most fractures were spontaneous. In line with the previous reports, the timing and severity of the fractures raise concern of DMAB discontinuation effect. Prolonged BP exposure in most of our patients challenges the protective effect hypothesis. Care providers, patients, and regulatory authorities should be aware of the possible risk of DMAB treatment interruption.

Hypercalcemia is caused by many different conditions and may lead to severe complications. Loss-of-function mutations of CYP24A1, encoding vitamin D-24-hydroxylase, have recently been identified in idiopathic infantile hypercalcemia and in adult kidney stone disease. The aim of this study was to investigate the genetics and clinical features of both infantile and maternal hypercalcemia.We studied members of four unrelated Israeli families with hypercalcemia, namely, one woman during pregnancy and after delivery and three infants. Clinical and biochemical data were obtained from probands' medical charts. Genomic DNA was isolated from peripheral blood and CYP24A1 was sequenced.Typical symptoms of hypercalcemia associated with the intake of recommended doses of vitamin D developed in the infants and pregnant woman. Four different loss-of-function CYP24A1 mutations were identified, two of which are reported here for the first time (p.Trp134Gly and p.Glu315*). The infants from families 1 and 2, respectively, were found to be compound heterozygotes, and the infant from family 3 and the pregnant woman were found to be homozygous.This is the first report of maternal hypercalcemia caused by a CYP24A1 mutation, showing that not only infants are at risk for this complication. Our findings emphasize the importance of recognition, genetic diagnosis and proper treatment of this recently identified hypercalcemic disorder in this era of widespread vitamin D supplements.

OBJECTIVE Previous studies assessing vitamin D status in adolescents with eating disorders showed inconsistent results. The aim of the current study was to assess vitamin D status in a large cohort of adolescent inpatients with eating disorders and its relation to bone mineral density (BMD) and depression. METHOD 25-Hydroxyvitamin D (25OHD), calcium, phosphorus, and alkaline phosphatase levels as well as BMD and depression were assessed on admission in 87 inpatients (aged 16 ± 2 years, females = 81) with eating disorders [anorexia nervosa (AN) = 64; bulimia nervosa (BN) = 5; eating disorders not otherwise specified-binge/purge type (EDNOS-B/P) = 18]. RESULTS Mean 25OHD levels were 24.1 ± 7.5 ng/ml (25.0 ± 7.6, 25.4 ± 9.9, and 22.0 ± 9.9 ng/ml in patients with AB, BN, and EDNOS-B/P, respectively). Vitamin D deficiency ( 32 ng/ml, considered optimal by some experts. No associations were found between 25OHD levels and BMD or comorbid depression. 25OHD levels during winter were significantly lower than summer levels (p < .001). Mean lumbar spine BMD z-score in patients with AN and EDNOS-B/P type was low (-1.5 ± 1.1) and correlated with body mass index standard deviation score (p = .03). DISCUSSION Adolescents with eating disorders show a high prevalence of vitamin D deficiency and insufficiency. Given the risk of osteoporosis in this population, 25OHD levels found in this group may not offer optimal bone protection. Vitamin D levels should be routinely checked and supplementation should be administered as required.

Background Procollagen C-proteinase enhancer 1 (PCPE1), a glycoprotein secreted from differentiating osteoblast, enhances the rate-limiting step of collagen type I fibrillar formation. It is expressed and secreted by cells that produce collagen type I and has the potential to be a marker for bone pathologies. Methods We developed an assay to quantify PCPE glycopattern based on isoelectric focusing (IEF) and detection with a bio-imaging camera (coefficient of variation within and between assays, 15% and 20%, respectively). Results PCPE was quantified in 39 serum samples from healthy subjects (17 females and 22 males). The concentration in the serum was 305(274) ng/ml, median(IQR). The level of the PCPE isoforms and their relative distribution were altered in patients with bone disorders. Conclusions The data generated by our system, support our hypothesis that combined data on PCPE concentration and isoforms may be useful for the diagnosis and follow-up of bone diseases. Further research, on larger cohorts of both normal subjects and patients, must be done.

Purpose Osteonecrosis of the jaw is a well-documented side effect of bisphosphonate (BP) use. Attempts have recently been made to predict the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ). We prospectively investigated the predictive value of serum levels of C-terminal telopeptide of collagen I (CTX), bone-specific alkaline phosphatase, and parathyroid hormone for the development of BRONJ. Patients and Methods Data on the demographics, comorbidities, and BP treatment were collected from 78 patients scheduled for dentoalveolar surgery. Of the 78 patients, 51 had been treated with oral BPs and 27 had been treated with frequent intravenous infusions of BPs. Blood samples for CTX, bone-specific alkaline phosphatase, and parathyroid hormone measurements were taken preoperatively. Surgery was performed conservatively, and antibiotic medications were prescribed for 7 days. Results Of the 78 patients, 4 patients taking oral BPs (7.8%) and 14 receiving intravenous BPs (51.8%) developed BRONJ. A CTX level less than 150 pg/mL was significantly associated with BRONJ development, with an increased odds ratio of 5.268 (P = .004). The bone-specific alkaline phosphatase levels were significantly lower in patients taking oral BPs who developed BRONJ. The parathyroid hormone levels were similar in patients who did and did not develop BRONJ. Conclusion The incidence of BRONJ after oral surgery involving bone is greater among patients receiving frequent, intravenous infusions of BPs than among patients taking oral BPs. Although the measurement of serum levels of CTX is not a definitive predictor of the development of BRONJ, it might have an important role in the risk assessment before oral surgery.

Background Knowledge about a disease provides professionals involved in its prevention and treatment with the information to make informed decisions about health practices. Gaps of knowledge regarding osteoporosis prevention and treatment have been found among different health professionals over the world, including nurses. Objectives The aim of this study was to assess a wider variety of aspects related to nurses' knowledge and attitudes regarding osteoporosis. Design A cross-sectional research design was used. Settings Two academic centers in the northern part of Israel. Participants A convenience sample of 158 registered nurses (mean age=39±10.3), attending classes at two academic centers. Methods Data were collected using a self-administered survey. Results Nurses were positive about their role and their skills for osteoporosis management, yet subjective and objective knowledge in different aspects of the disease was moderate. The average score of knowledge regarding risk factors for osteoporosis, as assessed by the Facts on Osteoporosis Quiz (FOOQ), was 17 (SD=3) out of 24, with female nurses, nurses working in Health Maintenance Organizations—HMOs, and nurses who underwent a bone density measurement scoring higher ( p Conclusions Nurses believed they have an important role in educating the public on osteoporosis prevention and management. Yet, their knowledge on different issues (e.g. signs of the disease, medication, and lifestyle issues) was only moderate. The only osteoporosis-related aspect they reported being confident about was advising on fall prevention. Measures should be taken in order to expand nurses' knowledge, such as education programs and postgraduate courses.

Contains fulltext : 52708.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To examine plasma homocysteine, vitamin B(12), and folate levels in females with restricting and bingeing/purging eating disorders (EDs). METHOD: Adolescent and adult female patients were compared to appropriate control groups with regard to plasma homocysteine levels. RESULTS: The plasma homocysteine level of the adult ED patients was higher than that of controls for all age groups examined. In adolescents, no significant difference was found comparing ED patients younger than 16 years of age to control data, whereas in the 16-20 year age group, the plasma homocysteine level was significantly higher among the ED group, regardless of the type of ED. Vitamin B(12) and folate levels were within normal limits in all ED groups. CONCLUSION: Elevated plasma homocysteine levels were found in adult and older adolescent female ED patients (but not in younger adolescents) compared to controls. This finding is not related to deficiencies in vitamin B(12) or folate.

The aim of this study was to assess Israeli dietitians' knowledge and attitudes regarding osteoporosis. Participants were 320 dietitians responding to a mail survey. Israeli dietitians scored highly on the Facts on Osteoporosis Quiz FOOQ. Israeli dietitians' dietary knowledge regarding calcium (recommended dietary allowance, content in food and in supplements) was fairly high; unlike knowledge regarding vitamin D. Israeli dietitians had a firm positive opinion of their role in the prevention and treatment of osteoporosis.

Background and aims: Health practices such as calcium-rich diet and exercise, are associated with the prevention of osteoporosis. Since studies showed that ethnic minorities are less involved in preventive practices, the aim of this study was to examine patterns and correlates of osteoporosis health-related behavior in Israeli-Jewish and Arab women. Methods: Interviews were conducted with 261 women aged 45 and older (70% Jewish). Health behavior included: physical activity, smoking, alcohol consumption, use of hormone replacement therapy, screening behavior, calcium intake, pharmacological prevention, and help-seeking patterns. Correlates included demographic variables, health characteristics (menopausal status, family history of osteoporosis), knowledge about osteoporosis, and beliefs (susceptibility and worries about developing osteoporosis). Results: Compared with Jewish participants, a lower percentage of Arab women engaged in physical activity, were on HRT, and had had bone density examinations. Their overall calcium intake was significantly lower as well. Levels of knowledge were moderate to low for the whole group, but more so among Arab women. Engaging in physical activities was associated with being menopausal and with having more knowledge among Jewish women, and with having more knowledge and lower rates of concern among Arab women. Conclusions: Expanding knowledge about osteoporosis may prove beneficial for increasing participation in preventive behavior in both groups. Special attention should be paid to different levels of education and to differences in subjects’ needs and accessibility to sources of information.

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.

To provide adequate and updated information regarding changes in health care regulations or policies can be a challenging task for policy makers. The aim of the present study was to examine knowledge about new regulations regarding publicly funded drugs for the treatment of osteoporosis in a group of 109 Israeli women. Participants were interviewed between 3 and 6 months after the new regulations were enacted. Although participants were aware of their eligibility, moderate levels of knowledge were found regarding the content of the regulations. Especially low levels of knowledge were found regarding the scope of services and the definition of osteoporosis according to the regulations. High-risk participants (i.e. older participants and those with lower T score or who had suffered a fracture) had no better knowledge of the regulations. The development of multifaceted information programs aimed at disseminating the content of policy changes is encouraged.

This study examines women's willingness to pay (WTP) for drug treatment for osteoporosis before and after the enactment of regulations approving public funding for the drugs and for a hypothetical more effective but not funded drug. One hundred and nine postmenopausal women recruited sequentially from a large bone metabolism outpatient clinic in central Israel were asked by telephone interview to report their maximum WTP out-of-pocket for a drug that would reduce the risk of hip fracture by 50% in four hypothetical cases varying by the level of risk described. Additionally, after the regulations, responses were elicited also for a hypothetical more effective drug. Information regarding participants' sociodemographic and health characteristics, as well as their knowledge of osteoporosis, was also collected. Women would pay considerable sums of money (between 85% to 124% of the price of the drugs) for osteoporosis treatment and these sums increase significantly as the risk of suffering a hip fracture increases. After the enactment of the regulations, women were still willing to pay 54% to 100% of the price of the drugs out-of-pocket. Increased WTP after the regulations was associated with increased ability to pay and to lower levels of knowledge of the disease. After the enactment, participants' WTP for a more effective drug was no different from their WTP for a less effective drug. WTP measures show relative stability over time. The dissemination of information regarding policy or regulatory changes should be encouraged in order to ensure rational decision-making processes.

Previous studies assessing vitamin D status in adolescents with eating disorders showed inconsistent results. The aim of the current study was to assess vitamin D status in a large cohort of adolescent inpatients with eating disorders and its relation to bone mineral density (BMD) and depression.25-Hydroxyvitamin D (25OHD), calcium, phosphorus, and alkaline phosphatase levels as well as BMD and depression were assessed on admission in 87 inpatients (aged 16 ± 2 years, females = 81) with eating disorders [anorexia nervosa (AN) = 64; bulimia nervosa (BN) = 5; eating disorders not otherwise specified-binge/purge type (EDNOS-B/P) = 18].Mean 25OHD levels were 24.1 ± 7.5 ng/ml (25.0 ± 7.6, 25.4 ± 9.9, and 22.0 ± 9.9 ng/ml in patients with AB, BN, and EDNOS-B/P, respectively). Vitamin D deficiency (15 ng/ml) was found in 7.8% of the patients, and insufficiency (15-20 ng/ml) in 22.2%. Only 16.7% had levels32 ng/ml, considered optimal by some experts. No associations were found between 25OHD levels and BMD or comorbid depression. 25OHD levels during winter were significantly lower than summer levels (p.001). Mean lumbar spine BMD z-score in patients with AN and EDNOS-B/P type was low (-1.5 ± 1.1) and correlated with body mass index standard deviation score (p = .03).Adolescents with eating disorders show a high prevalence of vitamin D deficiency and insufficiency. Given the risk of osteoporosis in this population, 25OHD levels found in this group may not offer optimal bone protection. Vitamin D levels should be routinely checked and supplementation should be administered as required.

This study, encompassing 2591 Israeli soldiers, characterized Israeli soldiers with stress fractures to profile individuals who are prone to experience stress fractures: 318 with clinically and scintigraphically proven high grade stress fractures; 237 soldiers with symptoms but with normal scintigraphy; and 2036 soldiers with no symptoms. Soldiers with high grade stress fractures weighed less (68.4 +/- 7.9 kg versus 70.5 +/- 12.4 kg), smoked less, and reported fewer previous stress fractures, had fewer reports of stress fractures in their family histories, and had fewer incidences of bone diseases than did control subjects. Serum levels of bone specific alkaline phosphatase and osteocalcin were elevated in patients with high grade stress fractures compared with control subjects with no symptoms: 37.6 versus 26.2 units/L, and 10.8 versus 8.8 ng/mL, respectively. Levels of 25-hydroxy vitamin D were lower in patients with high grade stress fractures (25.3 ng/mL) than in control subjects (29.8 ng/mL). This study revealed that several parameters can distinguish soldiers with high grade stress fractures, but their predictive value and precise pathogenetic role remain unclear.

Objective: We describe calcium homeostasis during pregestation and gestation in a woman with iatrogenic hypoparathyroidism, treated with continuous subcutaneous recombinant parathyroid hormone (PTH) (1–34) infusion.Results: The requirement for PTH did not fluctuate much during pregnancy and was essential for maintaining normal calcium and phosphorus serum levels.Conclusions: This study documents the insufficiency of PTH-related protein (PTHrP) or other gestation-related hormones to compensate for PTH deficiency in hypoparathyroid women, and the successful utilization of continuous subcutaneous recombinant PTH (1–34) infusion to achieve normal calcium homeostasis during gestation. Clinical trials with PTH replacement in such circumstances are warranted.

Changes in bone mineral density and bone strength following treatment with zoledronic acid (ZOL) were measured by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA). ZOL treatment increased spine and hip BMD vs placebo, assessed by QCT and DXA. Changes in trabecular bone resulted in increased bone strength.To investigate bone mineral density (BMD) changes in trabecular and cortical bone, estimated by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA), and whether zoledronic acid 5 mg (ZOL) affects bone strength.In 233 women from a randomized, controlled trial of once-yearly ZOL, lumbar spine, total hip, femoral neck, and trochanter were assessed by DXA and QCT (baseline, Month 36). Mean percentage changes from baseline and between-treatment differences (ZOL vs placebo, t-test) were evaluated.Mean between-treatment differences for lumbar spine BMD were significant by DXA (7.0%, p0.01) and QCT (5.7%, p0.0001). Between-treatment differences were significant for trabecular spine (p = 0.0017) [non-parametric test], trabecular trochanter (10.7%, p0.0001), total hip (10.8%, p0.0001), and compressive strength indices at femoral neck (8.6%, p = 0.0001), and trochanter (14.1%, p0.0001).Once-yearly ZOL increased hip and spine BMD vs placebo, assessed by QCT vs DXA. Changes in trabecular bone resulted in increased indices of compressive strength.

To characterize the relationship between occupational sun exposure and seasonal variations in serum 25-OH-D3, four consecutive measurements of 25-OH-D3, one per season, were taken in 122 outdoor and 104 indoor Israeli workers. Continuous UVB measurements, taken in Beer Sheva, Israel, provided the average daily standard erythema dose (SED) of ambient solar UVB. The average daily exposure of the outdoor and indoor workers to solar UVB was 4.4+/-1.6 h (4.0-37.6 SED) and 0.9+/-0.5 h (0.6-8.2 SED), respectively. At each season mean 25-OH-D3 were significantly higher among outdoor workers than among indoor workers. Mean 25-OH-D3 increased significantly from spring to autumn in both gender and occupational groups. Adjusting for confounders, high (>median) 25-OH-D3 among males was significantly associated with occupational sun exposure in the autumn (odds ratio [OR] 4.31; 95% confidence interval [CI] 1.4-13.3), and among females in the spring (OR 3.35; 95% CI 1.53-7.32). Among this working population optimal vitamin D status (>or=30 ng mL(-1)) was approached only in summer by males working either outdoor or indoor. In the rest of the year 25-OH-D3 ranged between >or=20.0 and 29.0 ng mL(-1). Monitoring 25-OH-D3 may disclose undesirable vitamin D status following reduced sun exposure for skin cancer prevention among outdoor workers.

To determine if chronic hypophosphatemia causes myocardial dysfunction, we explored one model for this metabolic derangement by prospectively investigating 11 patients (aged 5-18 years) with X-linked hypophosphatemic rickets (XLH) by M-mode, two-dimensional, and Doppler echocardiography. Inorganic phosphate and calcitriol (1,25-dihydroxyvitamin D3) treatment was withheld 72 h prior to study. None of the patients had cardiovascular symptoms. Fasting serum inorganic phosphate concentrations were subnormal in all: 2.6 + 0.5 mg/dl (SD). Serum total and ionized calcium, magnesium, sodium, potassium, and creatine kinase myocardial fraction (CK-MB) levels were unremarkable. Electrocardiograms revealed early repolarization abnormalities in 3 of the 11 patients: 1 had significant QT prolongation (corrected for heart rate), and 2 had T wave abnormalities. Exaggerated U waves occurred in 4 subjects. Resting echocardiograms were normal in 9 patients. In 1 subject there was mitral valve prolapse, and 1 patient possibly had an atrial septal defect (these findings were considered unrelated to hypophosphatemia). All M-mode measurements were normal. The two-dimensionally derived end-diastolic and end-systolic left ventricular volumes were 60.3 + 18.0 and 20.5 + 6.9 ml, respectively. Left ventricular ejection fraction was 66.1 + 4.7%, and the cardiac index by Doppler study was 4.1 + 0.8 liters/min per m2 (both values were within normal limits). Although the precise pathogenesis of XLH is unknown and our findings suggest that some electrocardiographic abnormalities may be common in this disorder, we found no evidence for left ventricular dysfunction in this human model of clinically significant long-standing hypophosphatemia.

Worldwide changes in the incidence, histological type, and prognosis of thyroid cancer (TC) have been observed. Regional differences in the spectrum of TC may be related to genetic factors, ionizing radiation, lifestyle, and nutritional iodine, as well as to the availability of medical services.Analysis of records of 5864 TC patients (diagnosed between 1982 and 2001), retrieved from the Israel National Cancer Registry.The age-standardized incidence rate (ASR per 100,000 persons) of TC among Jewish women in 2001 was 12.45 (higher than generally reported in the world) and 3.68 among Jewish men. There was a significant increase in the ASR for TC between 1982 and 2001 in the Jewish population (by 101% among women and by 25% among men, p0.01 for both), mainly due to papillary carcinoma. TC incidence increased in the non-Jewish population from 2.33 to 6.02 in women (p0.05) and from 1.13 to 2.49 in men (p0.05). TC incidence was similar among immigrants from Europe and America arriving in Israel before 1990 or after 1990 for both genders. An improved 5-year survival was noted in patients diagnosed between 1992 and 1996 in comparison to patients diagnosed earlier: 1982-1986 (86% versus 78%, p0.01).A marked increase in TC incidence over the last two decades (mainly due to papillary carcinoma) has been noted in different Israeli subpopulations, being the highest in Jewish women. The increase trends were similar regardless of gender or ethnicity. The reasons for this rise in TC incidence and improvement in the survival are probably multifactorial and may relate partly to increased diagnostic vigilance and changes in clinical practice.

Male hypogonadism is associated with low bone mineral density (BMD) and an increased risk of fractures. Testosterone replacement therapy improves BMD in young hypogonadal men. This effect is milder in older patients, who are at greater risk for fractures. We studied the effects of alendronate or placebo on BMD in 22 osteoporotic men, 29-69 years of age (mean, 50.2+/-11.2 years) with long-standing hypogonadism, receiving standard testosterone replacement treatment. Alendronate 10 mg daily (n=11) increased lumbar-spine BMD by 6.0 and 8.4% at 6 and 12 months, respectively, compared with -0.5% at 6 months and +3.3% at 12 months in the placebo group (n=11; P

Objective: To compare patterns of osteoporosis health-related behaviors in peri and postmenopausal ultra-orthodox and secular Jewish women. Methods: Interviews were conducted with 277 Israeli-Jewish women aged 45+. Health behaviors examined included: physical activity, smoking behavior, alcohol consumption, hormone replacement usage, screening behavior, calcium intake, pharmacological prevention, and help-seeking patterns. Correlates included demographic variables, health characteristics, knowledge, susceptibility beliefs, and familiarity with the disease. Results: Low proportions of women in both groups participated in physical activities, but differed in type. Calcium intake was deficient in both groups. Education was the only correlate of calcium intake among secular women, and previous experience with the disease was the main determinant among orthodox women. Compared with the secular group, a considerably lower proportion of orthodox women reported using HRT or having performed a bone density examination. Orthodox participants’ level of knowledge about osteoporosis was significantly lower as well. Education was an important correlate of knowledge in both groups, as was having performed a bone density examination. Higher age and being menopausal were important correlates of knowledge only for secular women. Having a family member suffering from the disease was associated with higher levels of knowledge among orthodox women. Marked differences were found in the participants’ sources of information across groups. Conclusions: Findings emphasize the need to expand education in all areas of osteoporosis health-related behaviors among ultra-orthodox women, and in calcium intake and exercise for secular women as well. The transmission of the information should be adapted to the practices of each group.

Mutations in WNK kinases cause pseudohypoaldosteronism type II (PHA II) and may represent a novel signaling pathway regulating blood pressure and K(+) and H(+) homeostasis. PHA II is an autosomal dominant disorder characterized by hypertension, hyperkalemia, and metabolic acidosis, with normal glomerular filtration rate. Thiazide diuretics correct all abnormalities. Inactivating mutations in the thiazide-sensitive NaCl cotransporter cause Gitelman syndrome, featuring hypotension, hypokalemia, and metabolic alkalosis plus hypocalciuria and hypomagnesemia. We investigated whether hypercalciuria and hypermagnesemia occurred in a large family with PHA II. Eight affected and eight unaffected members of a PHA II family with the Q565E WNK 4 mutation were studied. In affected members blood and urinary chemistry were measured on and off hydrochlorothiazide (HCTZ), and bone mineral density was determined. Marked sensitivity to HCTZ was found. A mean dose of 20 mg/d reduced mean blood pressure in the six hypertensive subjects by 54.3 (systolic) and 24.5 (diastolic) mm Hg. In affected subjects, HCTZ reduced mean serum K(+) by 1.12 mmol/liter, mean serum Cl(-) by 6.2 mmol/liter, and mean urinary calcium by 65% and elevated mean serum calcium by 0.11 mmol/liter and mean serum urate by 118 micromol/liter. Compared with the literature, this represents an increase of 6-7 in HCTZ potency. Affected members had normomagnesemia, hypercalciuria (336 +/- 113 vs. 155 +/- 39 mg/d in unaffected relatives, P = 0.0002), and decreased bone mineral density. In PHA II the observed marked sensitivity to thiazides and the hypercalciuria are consistent with increased NaCl cotransporter activity. PHA II may serve as a model to investigate thiazides' beneficial effects and side effects.

Genetic factors have been shown to play a major role in the development of peak bone mass, with hereditability accounting for about 50-85% of the variance in bone mass. Numerous candidate genes involved in osteoporosis have been proposed, but the precise genes and their relative contribution remain unknown.To gain insight into the genetic basis of idiopathic low bone mineral density in Israeli patients by analyzing the impact of two candidate genes: polymorphism of the vitamin D receptor gene and polymorphism A986S in the calcium-sensing receptor gene.We analyzed 86 Jewish Israeli patients with LBMD: 38 premenopausal women and 48 men, and compared the allelic pattern distribution with that of the general population (126 men and 112 women). Genotyping of the VDR gene was performed in three polymorphic sites using restriction enzymes, and allelic analysis of A986S polymorphism in the CaSR gene was performed using the denaturing gradient gel electrophoresis technique.In LBMD women the distributions of VDR alleles in Apal polymorphism were AA = 7/28, Aa = 16/28 and aa = 5/28; in Taql polymorphism TT = 10/31, Tt = 16/31 and tt = 5/31; and in Bsml polymorphism BB = 7/32, Bb = 14/32 and 11/32. In LBMD men the distributions were AA = 17/39, Aa = 21/39 and aa = 1/39; in Taql polymorphism TT = 12/42, Tt = 23/42 and tt = 7/42; and in Bsml polymorphism BB = 12/41 Bb = 18/41 and bb = 11/32. The distributions of all these polymorphisms in the control groups were not significantly different. Adjusting for the independent age and gender parameters confirmed that these three polymorphisms of the VDR gene did not have a significant effect on bone mineral density. Thirty percent (24/79) of LBMD patients of either sex displayed heterozygosity of the CaSR A986S polymorphism, compared with 40 of 203 controls (19.7%) (P = 0.059). Adjusting for age and gender in these patients revealed a significant difference in the femoral neck BMD between homozygotes and heterozygotes (p = 0.002). The age at menarche of the LBMD women was found to predict 61% of the variance of femoral neck BMD.In Israeli Jewish men and premenopausal women VDR gene alleles do not seem to be associated with lower lumbar spine or femoral neck BMD. A trend towards heterozygosity for a CaSR polymorphism missense mutation was noted in the LBMD patients. Age at menarche in the LBMD women was found to be an important predictor of BMD. A significant difference was found between LBMD women and healthy control women towards heterozygosity for a CaSR polymorphism, as well as between homozygotes and heterozygotes for a CaSR polymorphism in BMD. The significance of these findings and their applicability to a larger population awaits further studies.

Objective: The aim of the present study was to compare the beliefs, knowledge, and health-related behaviors of first-degree relatives (FDRs) of osteoporotic women with a comparison group of women not having a FDR with osteoporosis. Research design: Telephone interviews. Participants: Participants were 172 women (48 FDRs and 124 comparisons), recruited by a systematic sampling from the list of all women aged 40+ attending an outpatient screening program at a large tertiary medical center in Israel. Methods: Information was collected regarding participants' perceived susceptibility to develop osteoporosis, perceived concerns, and perceived prevention optimism. Additionally, information was collected regarding knowledge about osteoporosis, and participation in screening and preventive behavior. Results: Participants in the FDR group reported higher perceived susceptibility and higher concerns about developing the disease than participants in the comparison group. A higher proportion of FDRs reported engaging in screening behavior, but no differences were found in preventive behaviors. Screening behavior was associated with perceived concerns and age for members of the comparison group, and with age for FDRs. Conclusions: FDRs are characterized by greater perceived vulnerability and concerns. However, they are no more likely to engage in preventive behaviors or have more knowledge about the disease. These findings stress the importance of expanding efforts to increase the knowledge and awareness of at-risk persons.

Background and aims: Osteoporosis is the most common human bone disease. Although proper diagnosis may minimize injury and disability, this depends to a great extent on the knowledge and attitudes of physicians. The aim of the present study was to assess physicians’ attitudes, knowledge and practice regarding the diagnosis of osteoporosis. Methods: A questionnaire was mailed to 1900 Israeli physicians addressing their knowledge and attitudes about osteoporosis and its diagnosis, and their perceptions regarding the cost-effectiveness of different diagnostic methods. Results: Answers were received from 19% of the physicians. The majority of the respondents supported screening for osteoporosis, especially in high-risk women. Overall, the participants had good knowledge about the definition of osteoporosis and its risk factors, but poor knowledge about its prevalence. Female physicians had better knowledge and stronger attitudes than male physicians. Similarly, younger and less experienced physicians showed better knowledge. The majority of the participants reported being familiar with, and using all types of clinical methods. They also perceived these methods as highly cost-effective. Conclusions: Findings of the present study stress the need to extend the knowledge of physicians regarding diagnosis of osteoporosis and the research aimed at understanding their attitudes.

Familial hypocalciuric hypercalcemia (FHH) is often considered in the differential diagnosis of hyperparathyroidism, but is rarely diagnosed. So far, FHH has not been documented in Israel. This report presents preliminary evidence for the occurrence of FHH in Israel.

Sex hormone deficiency is the most common cause of bone loss. Reduced bone mass and an increased risk for osteoporotic fractures have been described in hypogonadal subjects of both sexes. We present here the results of treating two patients showing abnormal sexual differentiation (an XX male and an XY female), who suffered from bone loss related to sex hormone deficiency, with cross genotype sex hormones.Patient 1 was an asymptomatic 39-yr-old XY female with complete androgen insensitivity. Her testes had been removed, and she later discontinued estrogen treatment. Patient 2, a 37-yr-old XX male, had congenital adrenal hyperplasia, which led to a masculine phenotype. He was ovariectomized and reared as a male. He was treated with glucocorticoids but refused androgen treatment for many years. We treated both patients with phenotypically matched sex hormones (patient 1 received conjugated estrogens 1.25 mg/day, and patient 2 received 250 mg testosterone every 4 weeks) and followed their bone mineral density (BMD) using dual-energy X-ray absorptiometry, urine calcium, and hydroxyproline excretion.Before treatment both patients had low sex hormones and highly elevated gonadotropins. As a result of treatment urine hydroxyproline excretion decreased from 45 and 26.7 mg/g creatinine to 15 and 15.9 mg/g creatinine in patients 1 and 2 respectively. In patient 1, lumbar BMD rose from 0.912gr/cm2 to 0.976gr/cm2 and femoral neck BMD rose from 0.716gr/cm2 to 0.836gr/cm2 after 4 years of treatment. In patient 2, lumbar BMD rose from 0.717gr/cm2 to 0.815gr/cm2 and the femoral neck BMD rose from 0.509gr/cm2 to 0.635gr/cm2 after 27 months of treatment.Phenotypically-matched sex hormone therapy in patients with abnormal sexual differentiation is essential not only to maintain external appearance but also for the preservation of bone mass.

Dual energy radiography (DER) is a new technique for non-invasive measurement of vertebral bone mineral density, which because of its high precision (1%), is particularly suitable for prospective analyses of time-related changes in bone mass. However, we recently found that DER is less sensitive to demineralization of trabecular bone than quantitative computed tomography (QCT). Since the compact bone of the posterior vertebral elements are included in the standard anterior-posterior DER (APDER), but not in QCT measurements, changes in trabecular bone mass attending the early phases of the osteoporotic process go undetected with the APDER technique due to the preponderance of cortical mass. Lateral-view DER (LDER), however, would minimize the contribution of vertebral compact bone as well as intra-abdominal calcifications to the trabecular component. To determine the in vivo short-term precision of the LDER method, we obtained three measurements in 18 healthy women, aged 23 to 76, during a four-week period. In addition, both APDER and LDER measurements were obtained in 53 healthy women, aged 23 to 80. The coefficient of variation for LDER was 2.8%. LDER density values accounted for a higher percentage of the variance of bone mass measurements with age (47%) than APDER (23%). Moreover, LDER declined significantly with age in both premenopausal (r = -0.42, p less than 0.05) and post-menopausal women (r = -0.50, p less than 0.005), whereas the age-related changes in APDER values failed to reach statistical significance in either group. The rate of bone loss with age in the premenopausal group was 0.45% per year with LDER, and 0.10% per year with APDER. Postmenopausal women showed a 0.78% loss of bone mass per year with LDER and 0.47% per year with APDER. The correlation between APDER and LDER was significant (r = 0.78, p less than 0.01). The accumulated data indicate that LDER may be a more appropriate technique than APDER for detecting the initial loss of vertebral trabecular bone that characterizes early subclinical osteoporotic syndrome.

In previous studies, we showed that blood monocyte elaboration of interleukin 1 (IL-1), a known stimulator of bone resorption, was higher in osteoporotic patients with rapid bone turnover than in those with slow turnover and in nonosteoporotic subjects. Since an acceleration of bone loss following menopause contributes to the risk of osteoporosis in women, we have studied the effects of menopause and ovarian steroid treatment on IL-1 release by monocytes obtained from nonosteoporotic and osteoporotic women. IL-1 activity in the monocyte culture medium derived from untreated postmenopausal women (nonosteoporotic and osteoporotic) was higher than in the medium derived from either untreated premenopausal or estrogen/progesterone-treated postmenopausal women. A significant negative correlation was found between IL-1 and years since menopause in both the healthy (r = -0.75; P less than 0.005) and the osteoporotic (r = -0.61; P less than 0.01) untreated postmenopausal women. The difference between the two slopes was significant at P less than 0.05. Premenopausal IL-1 levels were achieved within 8 years of menopause in the nonosteoporotic, but not in the osteoporotic, subjects in whom increases were evident as long as 15 years after menopause. IL-1 also correlated inversely with vertebral mineral density (r = -0.37; P less than 0.05), as measured by quantitative computed tomography. In prospective studies, treatment with estrogen/progesterone for 1 month caused a substantial highly significant decrease in IL-1 activity in each of three nonosteoporotic and five osteoporotic women, confirming the apparent effect of hormone therapy observed in the cross-sectional analysis. Although a cause-effect relationship has not been established, it is our hypothesis, based on these data, that alterations in IL-1 production may underlie the postmenopausal acceleration in bone loss and its inhibition by ovarian steroids. Persistent elevation of IL-1 secretion appears to be a feature of postmenopausal osteoporosis.

introduction: Several reports suggest significantly reduced left ventricular performance in subjects with chronic hypocalcemia. We prospectively investigated eight patients, aged 13 to 31 years, with long-standing hypocalcemia due to idiopathic hypoparathyroidism or pseudohypoparathyroidism by echocardiography. patients and methods: Six subjects had symptomatic hypocalcemia manifested as recurrent tetany (four), seizures (four), mental retardation (three), behavior disorder (one), and skeletal abnormalities (four); three subjects were untreated when studied. None had carciovascular symptoms. Each patient underwent clinical, biochemical, and cardiac studies, including Doppler, two-dimensional, and M-mode echocardiography, on the same day. results: In serum, both total and ionized calcium concentrations were reduced and averaged 7.2 mg/dl (range: 5.3 to 8.5 mg/dl; normal: 9.0 to 10.3 mg/dl) and 3.6 mg/dl (range: 3.0 to 3.9 mg/dl; normal: 4.5 to 5.3 mg/dl), respectively. Electrocardiograms revealed prolonged QTc intervals in six patients. Also noted were prominent U waves (five), T-wave abnormalities (four), and right-axis deviation (one). Resting echocardiography, however, demonstrated normal left ventricular function in all subjects. All M-mode measurements were normal. Two-dimen-sional-derived left ventricular end-diastolic and end-systolic volumes were 87.1 ± 20.1 ml and 30.2 ± 9.7 ml (mean ± SD), respectively. Left ventricular ejection fraction was 65 percent (61.2 to 74.7 percent). Doppler-derived cardiac output and cardiac index averaged 5.1 liters/minutes (2.9 to 6.7 liters/minute) and 3.0 liters/minute/m2 (1.7 to 4.3 liters/minute/,2), respectively. conclusion: Our prospective study of eight subjects with functional hypoparathyroidism demonstrated that, despite electrocardiographic abnormalities, long-standing hypocalcemia was not associated with left ventricular dysfunction.