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Early brain injury (EBI) is the leading cause of poor prognosis for patients suffering from subarachnoid hemorrhage (SAH), particularly learning and memory deficits in the repair phase. A recent report has involved calcium/calmodulin-dependent protein kinase II (CaMKII) in the pathophysiological process underlying SAH-induced EBI. Alpha-asarone (ASA), a major compound isolated from the Chinese medicinal herb Acorus tatarinowii Schott, was proven to reduce secondary brain injury by decreasing CaMKII over-phosphorylation in rats' model of intracerebral hemorrhage in our previous report. However, the effect of ASA on SAH remains unclear, and the role of CaMKII in both acute and recovery stages of SAH needs further investigation. In this work, we first established a classic SAH rat model by endovascular perforation and intraperitoneally administrated different ASA doses (10, 20, and 40 mg/kg) 2 h after successful modeling. Then, the short- and long-term neurobehavioral performances were blindly evaluated to confirm ASA's efficacy against SAH. Subsequently, we explored ASA's therapeutic mechanism in both acute and recovery stages using histopathological examination, TUNEL staining, flow cytometry, Western-blot, double-immunofluorescence staining, and transmission electron microscopy (TEM) observation. Finally, KN93, a selective CaMKII inhibitor, was applied in oxyhemoglobin-damaged HT22 cells to explore the role of CaMKII in ASA's neuroprotective effect. The results demonstrated that ASA alleviated short- and long-term neurological dysfunction, reduced mortality and seizure rate within 24 h, and prolonged 14-day survival in SAH rats. Histopathological examination showed a reduction of neuronal damage and a restoration of the hippocampal structure after ASA treatment in both acute and recovery phases of SAH. In the acute stage, the Western-blot and flow cytometer analyses showed that ASA restored E/I balance, reduced calcium overload and CaMKII phosphorylation, and inhibited mitochondrion-involved apoptosis, thus preventing neuronal damage and apoptosis underlying EBI post-SAH. In the recovery stage, the TEM observation, double-immunofluorescence staining, and Western-blot analyses indicated that ASA increased the numbers of synapses and enhanced synaptic plasticity in the ipsilateral hippocampi, probably by promoting NR2B/CaMKII interaction and activating subsequent CREB/BDNF/TrkB signaling pathways. Furthermore, KN93 notably reversed ASA's neuroprotective effect on oxyhemoglobin-damaged HT22 cells, confirming CaMKII a potential target for ASA's efficacy against SAH. Our study confirmed for the first time that ASA ameliorated the SAH rats' neurobehavioral deterioration, possibly via modulating CaMKII-involved pathways. These findings provided a promising candidate for the clinical treatment of SAH and shed light on future drug discovery against SAH., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Hypertension is a burden for most kidney transplant recipients. Whether respect of hypertension guidelines results in better outcomes is unknown., Methods: In this multicenter study, office blood pressure at 12 months following transplantation (i.e., after > 20 outpatient visits), and survival were assessed over 35 years among 2004 consecutive kidney transplant recipients who received a first kidney graft from 1985 to 2019 (follow-up: 26,232 patient-years)., Results: Antihypertensive medications were used in 1763/2004 (88.0%) patients. Renin-angiotensin-system blockers were used in 35.6% (47.1% when proteinuria was > 0.5 g/day) and calcium-channel blockers were used in 6.0% of patients. Combined treatment including renin-angiotensin-system-blockers, calcium-channel blockers and diuretics was used in 15.4% of patients receiving ≥ 3 antihypertensive drugs. Blood pressure was controlled in 8.3%, 18.8% and 43.1%, respectively, depending on definition (BP < 120/80, < 130/80, < 140/90 mmHg, respectively) and has not improved since the year 2001. Two-thirds of patients with uncontrolled blood pressure received < 3 antihypertensive classes. Low sodium intake < 2 g/day (vs ≥ 2) was not associated with better blood pressure control. Uncontrolled blood pressure was associated with lower patient survival (in multivariable analyses) and graft survival (in univariate analyses) vs controlled hypertension or normotension. Low sodium intake and major antihypertensive classes had no influence on patient and graft survival., Conclusions: Pharmacological recommendations and sodium intake reduction are poorly respected, but even when respected, do not result in better blood pressure control, or patient or graft survival. Uncontrolled blood pressure, not the use of specific antihypertensive classes, is associated with reduced patient, and to a lesser extent, reduced graft survival, even using the 120/80 mmHg cut-off., (© 2023. The Author(s) under exclusive licence to Italian Society of Nephrology.)

This national register study investigated osteoporosis medication prescriptions for secondary fracture prevention among older Swedish adults. Although prescription proportions are increasing for both men and women, they remain low, especially among individuals aged 90 and older. Improved Fracture Liaison Services could increase the prescription proportions and should be bolstered., Purpose: Despite clear guidelines for secondary fracture prevention among older adults, it seems undertreatment persists. We aimed to describe secondary fracture prevention with medical osteoporosis treatment in the older Swedish population. Specifically, how prescription has changed over time and if these patterns differ in sociodemographic subgroups., Methods: Between 2007 and 2020, osteoporosis medication use was studied among all Swedish residents aged 70 and older who had a fragility fracture in the previous 5 years. Previous fragility fractures were defined as fractures of the humerus, wrist, hip, or vertebrae. Osteoporosis medication was defined as any prescription of bone-enhancing medications (including bisphosphonates and denosumab)., Results: Osteoporosis medication increased over the study period, especially among men. Prescription among individuals 90 + was consistently two- to threefold lower compared to 70-79- and 80-89-year-olds. In 2018-2020, 8-17% of women and 5-9% of men, depending on age, received osteoporosis medication. At the beginning of the study period, women with higher education were more likely to be prescribed osteoporosis medication, though this difference decreased over time. Prescription of vitamin D and/or calcium as the only treatment was more common than osteoporosis medications throughout the study period., Conclusion: Despite increasing prescription proportions, medical treatment for secondary fracture prevention remains low. In addition, it is more common to be prescribed vitamin D or calcium than osteoporosis medication after a fragility fracture, contrary to current guidelines. These results indicate that there is room for improvement for Fracture Liaison Services in Sweden., (© 2023. The Author(s).)

This study assessed whether vitamin K, given with oral bisphosphonate, calcium and/or vitamin D has an additive effect on fracture risk in post-menopausal women with osteoporosis. No difference in bone density or bone turnover was observed although vitamin K 1 supplementation led to a modest effect on parameters of hip geometry., Purpose: Some clinical studies have suggested that vitamin K prevents bone loss and may improve fracture risk. The aim was to assess whether vitamin K supplementation has an additive effect on bone mineral density (BMD), hip geometry and bone turnover markers (BTMs) in post-menopausal women with osteoporosis (PMO) and sub-optimum vitamin K status receiving bisphosphonate, calcium and/or vitamin D treatment., Methods: We conducted a trial in 105 women aged 68.7[12.3] years with PMO and serum vitamin K 1  ≤ 0.4 µg/L. They were randomised to 3 treatment arms; vitamin K 1 (1 mg/day) arm, vitamin K 2 arm (MK-4; 45 mg/day) or placebo for 18 months. They were on oral bisphosphonate and calcium and/or vitamin D. We measured BMD by DXA, hip geometry parameters using hip structural analysis (HSA) software and BTMs. Vitamin K 1 or MK-4 supplementation was each compared to placebo. Intention to treat (ITT) and per protocol (PP) analyses were performed., Results: Changes in BMD at the total hip, femoral neck and lumbar spine and BTMs; CTX and P1NP did not differ significantly following either K 1 or MK-4 supplementation compared to placebo. Following PP analysis and correction for covariates, there were significant differences in some of the HSA parameters at the intertrochanter (IT) and femoral shaft (FS): IT endocortical diameter (ED) (% change placebo:1.5 [4.1], K 1 arm: -1.02 [5.07], p = 0.04), FS subperiosteal/outer diameter (OD) (placebo: 1.78 [5.3], K 1 arm: 0.46 [2.23] p = 0.04), FS cross sectional area (CSA) (placebo:1.47 [4.09],K 1 arm: -1.02[5.07], p = 0.03)., Conclusion: The addition of vitamin K 1 to oral bisphosphonate with calcium and/or vitamin D treatment in PMO has a modest effect on parameters of hip geometry. Further confirmatory studies are needed., Trial Registration: The study was registered at Clinicaltrial.gov:NCT01232647., (© 2023. The Author(s).)

Purpose of Review: Coronary artery calcium (CAC) is an important measure of subclinical atherosclerosis and strongly predicts atherosclerotic cardiovascular disease (ASCVD) outcomes. The purpose of this review is to discuss the key studies that have helped to establish its role as an important screening tool and its place in preventive cardiology., Recent Findings: Epidemiologic studies document a strong relation of age, race/ethnicity, and risk factors with the prevalence and extent of CAC. Large-scale registry and prospective investigations show CAC to be the strongest subclinical disease predictor of ASCVD outcomes, with higher CAC scores associated with successively higher risks and those with a CAC score of 0 having a long-term "warranty" against having events. Moreover, CAC is associated with greater initiation of preventive health behaviors and therapy. Current US guidelines utilize CAC to inform the treatment decision for statin therapy. Further study is underway to document whether CAC screening will ultimately improve clinical outcomes. CAC is well established as the most important subclinical cardiovascular disease measure for prediction of future ASCVD outcomes and can be used for informing the treatment decision for preventive therapies., (© 2022. The Author(s).)

Background: Hypertension is an important prognostic predictor in patients with chronic kidney disease (CKD), and the recommended target blood pressure has been continuously revised. This study aimed to reveal the current antihypertensive practices in Japanese patients with CKD., Methods: In the Fukuoka Kidney disease Registry, we extracted 3664 non-dialysis-dependent patients with CKD. Apparent treatment-resistant hypertension (aTRH) was defined as a failure of blood-pressure control treated with three antihypertensive medication classes or a treatment with ≥ 4 classes regardless of blood pressure. The blood-pressure control complied with the target blood pressure recommended by the KDIGO 2012 guideline., Results: The median age of the patients was 67 years, body mass index (BMI) was 23 kg/m 2 , and estimated glomerular filtration rate (eGFR) was 40 mL/min/1.73 m 2 . The number of patients with unachieved blood-pressure control was 1933, of whom 26% received ≥ 3 classes of antihypertensive medications. The first choice of medication was renin-angiotensin system inhibitors, followed by calcium-channel blockers. The rate of thiazide use was low in all CKD stages (3-11%). The prevalence of aTRH was 16%, which was significantly associated with BMI (odds ratio [95% confidence interval] per 1-standard deviation change, 1.38 [1.25-1.53]), decreased eGFR (1.87 [1.57-2.23]), as well as age, diabetes mellitus, and chronic heart disease., Conclusions: Renal dysfunction and obesity are important risk factors of aTRH. Even under nephrologist care, most patients were treated with insufficient antihypertensive medications. It is important to prescribe sufficient classes of antihypertensive medications, including diuretics, and to improve patients' lifestyle habits., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

Osteoporosis is often untreated especially in older people. This study found a low prescribing rate of osteoporosis treatment medication of 22.4% in older people admitted under the hip-fracture pathway. Factors associated with greater odds of being prescribed osteoporosis medications are categorized into patient-related, physician-related and system-related factors., Introduction: Osteoporosis represents a growing healthcare problem which is often overlooked by healthcare providers and untreated especially in older people. This study aims to assess the rate of osteoporosis treatment initiation and to investigate underlying physician and system-related barriers in geriatric patients admitted for hip fracture., Methods: A retrospective study was conducted on patients aged 60 years and older, admitted under the hip-fracture pathway from January 2019 to December 2019. Data collected included demographics, co-morbid conditions and laboratory data. Clinical charts were reviewed for whether bone mineral density (BMD) scan has been ordered, plans for bone health were made and reflected in the discharge summary, and if appropriate memos were written. The primary outcome was the prescription of osteoporosis treatment medications. Prescription lists were also reviewed for prescribing patterns of calcium and vitamin D., Results: A total of 375 patients older than 60 years old were identified. 281 patients who fit the inclusion and exclusion criteria with complete data were further analysed. Within 1 year of hip fracture admission, 63 (22.4%) of them were prescribed with osteoporosis treatment. Multivariate logistic regression identified milder stage of CKD (p = 0.038, OR = 0.617, 95% CI 0.392-0.973) and BMD scan performed (p &lt; 0.001, OR = 6.515, 95% CI 3.180-13.348) as independent factors associated with the prescription of osteoporosis treatment within 1 year of hip fracture admission., Conclusion: The rate of osteoporosis treatment initiation post-hip fracture is low. Systematic solutions will need to be established to ensure that osteoporosis treatment is addressed prior to discharge., (© 2022. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Due to the high burden of fragility fractures, we developed an interdisciplinary FLS care pathway for early management and monitoring of older adults discharged from a high-volume trauma center after hip fracture repair. Interdisciplinary FLS effectively improves up to 1-year adherence to treatments for secondary prevention of fragility fractures, reduces health facility admission, and improves long-term survival., Purpose: To compare adherence to secondary fragility fracture prevention, falls, healthcare facility admissions, and mortality between hip fracture older adults who entered the fracture liaison services pathway of care (FLS-CP) and those managed according to the usual traumatologist model of care (U-CP)., Methods: Prospective observational study enrolling subjects aged ≥ 65 years discharged by high-volume trauma center after hip fracture repair from February 2016 to February 2017, who consecutively entered FLS-CP or U-CP according to their preference and goals., Results: Compared to U-CP, those in FLS-CP had higher initiation rate and up to 1-year adherence to secondary prevention of fragility fracture, including vitamin D and calcium (87.7% vs 36.9%; p &lt; 0.0001), specific anti-osteoporosis drugs (75.1% vs 8.0%; p &lt; 0.0001), and complete anti-fracture therapy (72.3% vs 5.7%; p &lt; 0.0001). Older adults belonging to FLS-CP showed a lower likelihood of healthcare facility admission (RR 0.597; 95% CI 0.398-0.895; p = 0.0125), with a longer re-hospitalization-free survival (176.4 vs 88.7 days; p = 0.0152) than those in U-CP. One-year incidence of falls and fractures was similar between groups, with a lower tendency of the subjects in the FLS-CP to be multiple fallers (19% vs 34.8%; OR 0.057; 95% CI 0.004-0.876; p = 0.0690). The FLS-CP group experienced a lower 1-year (87.2% vs 74.3%; p = 0.001) and 3-year mortality (67.9% vs 55.6%; p = 0.0245) and a lower adjusted 5-year mortality hazard ratio (50.2% vs 58%; HR = 0.76; 95% CI 0.60; 0.96)., Conclusion: The FLS-CP may improve initiation and adherence to secondary prevention of fragility fractures, reduces healthcare facility admission, and improves long-term survival., (© 2022. The Author(s).)

Purpose: Hyperuricemia is common among patients with chronic kidney disease (CKD). In the general population, hyperuricemia is associated with secondary hyperparathyroidism (SHPT), in a mechanism that involves vitamin D metabolism. Data for patients with CKD, however, are scarce. We aimed to evaluate the relationship between hyperuricemia and mineral and bone metabolism, particularly hyperparathyroidism., Methods: This is a retrospective study that included 922 adult patients with stages 3, 4, or 5 CKD, not on dialysis. Clinical, demographic, and biochemical data were collected from charts and included uric acid, parathyroid hormone (PTH), 25(OH)-vitamin D, calcium, phosphate, renal function (estimated glomerular filtration rate-eGFR), and medications such as allopurinol, furosemide, and cholecalciferol. SHPT was defined as PTH > 65 pg/ml., Results: Our patients were mostly Caucasian women, with a mean age of 64 ± 16 years. SHPT and hyperuricemia were observed in 70% and 62.4% of patients, respectively. Patients with SHPT presented higher levels of uric acid (7.2 ± 1.8 vs. 6.6 ± 1.7 mg/dL, p = 0.0001) and a higher frequency of hyperuricemia (66% vs. 33%, p = 0.0001). Patients with hyperuricemia were mostly female, with lower eGFR, higher phosphate, and higher PTH. The risk of hypovitaminosis D was higher among patients with SHPT (69.7% vs. 53.1%, p = 0.0001). Hyperuricemia remained independently associated with hyperparathyroidism, (p = 0.033) even after adjustments for eGFR, calcium, phosphate, hypovitaminosis D, and use of allopurinol, calcitriol, furosemide, and cholecalciferol., Conclusion: Hyperuricemia seems to be a contributing factor for SHPT in patients with CKD. The mechanisms behind this finding have yet to be elucidated., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: Conventional therapy (calcium and activated vitamin D) does not restore calcium homeostasis in patients with chronic hypoparathyroidism (HypoPT) and is associated with renal complications and reduced quality of life (QoL). The aim of this study was to evaluate in a case-control, cross-sectional study, the rate of renal complications and QoL in two sex- and age-matched cohort of patients with differentiated thyroid cancer with (n = 89) and without (n = 89) chronic post-operative HypoPT (PoHypoPT) and their relationship with the biochemical control of the disease., Methods: Serum and urinary parameters, renal ultrasound and QoL were assessed by SF-36 and WHO-5 questionnaires., Results: Forty-three (48.3%) PoHypoPT patients reported symptoms of hypocalcemia. Twenty-six (29.2%) patients were at target for all 6 parameters, 46 (51.6%) for 5. The most frequently unmet targets were gender-specific 24-h urinary calcium (44.9%) and serum calcium (37.1%). Serum phosphate, magnesium and 25(OH)D were in the normal range in > 90% of patients. Renal calcifications were found in 26 (29.2%) patients, with no correlation with 24-h urinary calcium. eGFR did not differ between patients and controls. Conversely, patients had a significant higher rate of renal calcifications and a lower SF-36, but not WHO-5, scores. SF-36 scores did not differ between PoHypoPT patients who were, or not, hypocalcemic., Conclusions: Our study shows that the rate of renal calcifications was higher in patients with PoHypoPT than in those without. This finding, together with the reduced QoL and the presence of hypocalcemic symptoms in about half patients, underscores that the treatment of chronic HypoPT with conventional therapy is suboptimal., (© 2021. Italian Society of Endocrinology (SIE).)

In this study, we found that patients with hypoparathyroidism had a problem with calcium medication compliance, and this problem increased with the duration of the disease. We also showed that patients are concerned about the possible side effects of drugs., Introduction: In this study, we aimed to evaluate adherence to active vitamin D and calcium replacement in patients with post-surgical hypoparathyroidism., Methods: To elucidate the medication adherence, we performed a questionnaire survey using the six-item "Medication adherence questionnaire"(MAQ). The first, second, and sixth questions reflect the motivation status of the patients whereas the third, fourth, and fifth questions reflect the knowledge about the medication that is received. The responses are scored and patients are classified regarding their motivation to and knowledge about the particular drug., Results: Totally, 64 patients (male: 12/female: 52; mean age 48.6±11.6 years) who had post-operative hypoparathyroidism were included in our study. Median disease durance was 60 months (min-max: 12-295 months). We found that motivation score of calcium usage was significantly lower compared to vitamin D usage (p<0.001). The calcium motivation score was reversely correlated with disease duration (r= -0.256 and p=0.046). The most common worry about calcium usage was nephrotoxicity, and the most common worries about calcitriol treatment were kidney damage and polyuria. One-third of the patients were taking oral calcium and calcitriol less than the recommended dose., Conclusion: One-third of patients lack motivation to use calcium whereas half of the patients experiences anxiety about drug-related side effects. This is a preliminary study showing that vital calcium and active vitamin D intake may be interrupted due to side effect anxiety., (© 2022. International Osteoporosis Foundation and National Osteoporosis Foundation.)

As a result of the current demographics, increased projections of osteoporosis (OP) and prevalence of the disease in Turkey, a panel of multidisciplinary experts developed a thorough review to assist clinicians in identifying OP and associated fracture risk patients, diagnosing the disease with the appropriate available diagnostic methods, classifying the disease, and initiating appropriate treatment. The panel expects to increase the awareness of this prevalent disease, decrease consequences of OP with corresponding cost savings and, ultimately, decrease the overall burden of OP and related fractures in Turkey., Background: OP is not officially accepted as a chronic disease in Turkey despite the high prevalence and predicted increase in the following years. However, there are areas where the country is performing well, such as having a country-specific fracture risk assessment model, DXA access, and the uptake of FRAX. Additional efforts are required to decrease the existing treatment gap estimating 75-90% of patients do not receive pharmacological intervention for secondary prevention, and the diagnosis rate is around 25%., Methods: A selected panel of Turkish experts in fields related to osteoporosis was provided with a series of relevant questions to address prior to the multi-day conference. Within this conference, each narrative was discussed and edited by the entire group, through numerous drafts and rounds of discussion until a consensus was achieved. Represented in the panel were a number of societies including The Turkish Osteoporosis Society, The Society of Endocrinology and Metabolism of Turkey (SEMT), and The Turkish Society of Physical Medicine and Rehabilitation., Results: Standardized general guidelines to identify OP and related fractures and at-risk population in Turkey, which will enable clinicians to accurately and effectively diagnose the disease, treat the appropriate patients with available pharmacological and non-pharmacological treatments and decrease the burden of the disease., Conclusions: This manuscript provides a review of the current state of OP and related fractures in Turkey. Moreover, this manuscript reviews current international guidelines and national studies and proposes a number of helpful country-specific classifications that can be used by healthcare providers caring for the at-risk population. Additionally, the panel proposes practical recommendations that should be implemented nationally in order to decrease the burden of OP and related fractures and effectively preventing the burden in future generations.

Persistence and compliance to osteoporosis medications aiming to prevent fragility fractures are essential for fracture prevention, but are suboptimal in the population. A Fracture Liaison Service with a systematic follow-up led to ongoing therapy and optimal drug compliance for more than half of treated patients over 2 years., Purpose: Fracture Liaison Services (FLS) have the potential to improve persistence and compliance to osteoporosis therapy. We aimed to assess patterns of drug use in a high-level intervention FLS., Methods: Women and men (> 40 years) with a fragility fracture were recruited in a FLS, where osteoporosis therapy was prescribed if appropriate. Based on claims data, patients who filled their prescription in the 3-month period following baseline were selected. The 1- and 2-year persistence rates were measured using survival analysis. In non-persistent subjects, 1-year treatment re-initiation was measured. The 1- and 2-year compliance levels were measured, using the proportion of days covered (PDC > 80% = compliant). Regression analyses were performed to identify predictors of non-persistence/compliance., Results: Out of 332 subjects with complete drug insurance coverage, 297 (89.5%) were prescribed osteoporosis therapy by the FLS, and 275 (92.6%) were dispensed. Two hundred sixty participants (86.9% female; mean age 65.6 years) were selected for having filled a prescription inside 3 months after baseline. The 1- and 2-year persistence rates were 66.4% and 55.6%, respectively. Treatment re-initiation was observed in 56% of non-persistent patients. PDC was > 80% in 64.2% for 1 year and 62.5% for 2 years. Older and younger age, smoking, higher spine bone mineral density, lower major FRAX risk, and missing follow-up visits were predictors of non-persistence and/or non-compliance., Conclusions: After 2 years in a high-level intervention FLS, more than half the treated participants were persistent and compliant to treatment. Comparative effectiveness studies must be undertaken to determine whether this intervention is an improvement over usual care.

A guidance on the assessment and treatment of postmenopausal women at risk from fractures due to osteoporosis was recently published in Osteoporosis International as a joint effort of the International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (Kanis et al. Osteoporos Int, https://doi.org/10.1007/s00198-018-4704-5 , 2018). This manuscript updates the previous guideline document, published in 2013 (Kanis et al. Osteoporos Int 24:23-57, 2013) and is written from a European perspective. The present article reports and summarizes the main recommendations included in this 2018 guidance document (Fig. 1).

Purpose: To examine the prevalence and risk factors for hypercalcemia among non-dialysis chronic kidney disease (CKD) patients with mineral and bone disorder (MBD)., Methods: A retrospective cohort study was conducted in Singapore General Hospital, involving all CKD stage 4 and 5 pre-dialysis patients who were on treatment for MBD in June 2016. Each patient was followed up for 1 year and screened for hypercalcemia episodes. Mild, moderate and severe hypercalcemia were defined as corrected calcium of 2.47-3.00, 3.01-3.50 and ≥ 3.51 mmol/l respectively. Patients who were on dialysis, post-renal transplant, post-parathyroidectomy or had no calcium levels taken during the study period were excluded. Details related to patients' clinical information and hypercalcemia episodes were collected. Multivariate logistic regression analysis was performed to evaluate risk factors for hypercalcemia., Results: Of 557 patients, 75 (13.4%) patients developed hypercalcemia. There were 120 (97.6%) mild and 3 (2.4%) moderate hypercalcemia episodes. The daily elemental calcium intake from phosphate binders and usage of vitamin D analogues did not differ between patients with and without hypercalcemia (p > 0.05). After adjusting for covariates, lower baseline iPTH level [odds ratio (OR) 0.96, 95% CI 0.93-0.99], history of hypercalcemia in past 1 year (OR 11.11, 95% CI 3.36-36.75) and immobility (OR 3.34, 95% CI 1.34-8.40) were associated with increased hypercalcemia risk., Conclusion: Hypercalcemia affects a significant proportion of pre-dialysis patients with MBD. More studies should be undertaken to evaluate other risk factors associated with hypercalcemia.

Purpose: To evaluate adherence to European Society of Endocrinology guidelines and risk of renal complications in patients with chronic post-operative hypoparathyroidism (PO-HypoPT) treated with calcium and activated vitamin D metabolites., Methods: We evaluated 90 adult patients (68 females and 22 males) with chronic (3 years) PO-HypoPT. Total albumin-corrected (Alb-Ca) and ionized serum calcium, phosphate, creatinine, PTH, and 24-h urinary calcium were measured; renal ultrasound was also performed. Healthy hospital employers (n = 142) were used as control., Results: Complete data were available in 82 patients. Twenty-eight (34.1%) met four targets (Alb-Ca, phosphate, calcium phosphate product and 24-h urinary calcium), 36 (43.9%) three, 17 (20.7%) two, and 1 (1.2%) one. Thirteen (14.4%) had Alb-Ca value below and 18 (20.0%) above the target range and 54.9% 24-h urinary calcium above the upper normal limit. Seven (7.7%) has increased serum phosphate and none an increased calcium phosphate product. Eleven (12.2%) patients had eGFR < 60 mL/min × 1.73 m 2 . Nephrolithiasis was present in 27 (30%) patients. Compared with the controls, patients had lower Alb-Ca (8.9 ± 0.5 vs. 9.5 ± 0.3 mg/dL, P 0.0001) and a higher rate of kidney stones, mostly asymptomatic [27/90 (30%) vs 7/142 (5%), P < 0.0001, odd ratio 8.2 (3.4-19.9)]. Fifty-seven patients had ≥ four serum Ca 2+ determinations during follow-up. Forty (70.2) patients had values within the target range in > 50% of cases, 18 in > 75%, and only 2 in 100%. Two patients never had values in the target range., Conclusions: Treatment of chronic PO-HypoPT with calcium and activated vitamin D metabolites is suboptimal and associated with an increased risk of renal complications.

Background: Renal hyperparathyroidism is a common complication of chronic kidney disease (CKD). Parathyroidectomy (PTX) for these patients continues to be a valuable option in the era of calcimimetics. Postoperative hypocalcemia is common after surgery. The aim of this study was to identify clinical factors to define postoperative calcium requirements., Methods: From February 2013 to May 2017, 68 patients with chronic kidney disease 5 (CKD5) who underwent PTX were reviewed. We collected clinical and laboratory data preoperatively and calculated the total calcium requirement in a week after surgery. Univariate and multiple analyses were performed to study whether these clinical and laboratory factors were associated with calcium requirement., Results: Univariate analysis showed that preoperative alkaline phosphatase (ALP), calcium (Ca), parathyroid hormone and hemoglobin were independently associated with calcium requirement. Multivariate model showed that the preoperative ALP was the only independent factor that could predict the requirement of calcium., Conclusions: In the context of a high dCa (1.75 mmol/l) and a stable dose of calcitriol, preoperative ALP levels were significantly associated with calcium requirement in patients with CKD5 undergoing PTX.

Background: Hyperkalemia is prevalent in end-stage renal disease patients, being involved in life-threatening arrhythmias. Although polystyrene sulfonate (PS) is commonly used for the treatment of hyperkalemia, direct comparison of effects between calcium and sodium PS (CPS and SPS) on mineral and bone metabolism has not yet been studied., Methods: In a randomized and crossover design, 20 pre-dialysis patients with hyperkalemia (>5 mmol/l) received either oral CPS or SPS therapy for 4 weeks., Results: After 4-week treatments, there was no significant difference of changes in serum potassium (K) from the baseline (ΔK) between the two groups. However, SPS significantly decreased serum calcium (Ca) and magnesium (Mg) and increased intact parathyroid hormone (iPTH) values, whereas CPS reduced iPTH. ΔiPTH was inversely correlated with ΔCa and ΔMg (r = -0.53 and r = -0.50, respectively). Furthermore, sodium (Na) and atrial natriuretic peptide (ANP) levels were significantly elevated in patients with SPS, but not with CPS, whereas ΔNa and ΔANP were significantly correlated with each other in all the patients. We also found that ΔNa and Δ(Na to chloride ratio) were positively correlated with ΔHCO 3 - . In artificial colon fluid, CPS increased Ca and decreased Na. Furthermore, SPS greatly reduced K, Mg, and NH 3 ., Conclusion: Compared with SPS, CPS may be safer for the treatment of hyperkalemia in pre-dialysis patients, because it did not induce hyperparathyroidism or volume overload.

Osteoporosis and chronic kidney disease (CKD) have both independently important potential impact on bone health. A significant number of patients with CKD stages 3a-5D have been shown to have low bone mineral density (BMD), leading to a strikingly elevated risk of fractures (mainly hip fractures) and higher associated morbidity and mortality. Mechanical properties of bone beyond age and menopausal status are additionally affected by intrinsic uremic factors. Therefore, we review in this article not only general concepts of osteoporosis and related consequences, but also the diagnostic and therapeutic implications of low BMD and bone fractures in CKD, beyond increased vascular calcification. Antiresorptive agents (mainly bisphosphonates) were not previously recommended when the estimated glomerular filtration rate (GFR) was lower than 30 ml/min/1.73 m 2 . However, post-hoc analysis of large randomized clinical trials found that these drugs (i.e. alendronate, ribandronate, denosumab) had comparable efficacy in improving BMD and reducing fracture risk in individuals (mainly women) with moderate reductions of GFR (mostly CKD stages 3-4). Therefore, at least in the absence of clear abnormalities of CKD-related mineral metabolism disturbances, bone antiresorptive agents (and maybe anabolic agents) that are or will be approved for general osteoporosis may be appropriate for CKD. Nephrologists should probably not ignore any longer fracture risk assessment, especially in patients with additional risk factors for osteoporosis if results will impact treatment decisions. However, although different therapeutic agents have been shown to reduce the risk of fracture in CKD patients with low BMD, specific prospective studies, with or without bone biopsies, in CKD are urgently needed.

While the function of vitamin D in regulating calcium homeostasis is well established, there has been growing interest in its role in the prevention of numerous chronic diseases, including cardiovascular disease (CVD). There is mounting epidemiological evidence suggesting that vitamin D deficiency is linked to increased CVD risk. However, the results of previous vitamin D supplementation trials have yielded mixed results in regards to cardiovascular health, and the results of ongoing large-scale randomized controlled trials are not yet available. Further complicating the issue, calcium supplementation, which is often prescribed concurrently with vitamin D, has been associated with increased CVD risk in some (but not all) studies. Thus, it is currently unclear whether vitamin D supplements, particularly for those that are deficient, can help prevent the development of CVD. In addition, there has not been uniform consensus regarding the threshold of 25-hydroxyvitamin D levels that constitutes "sufficiency" across organizational guidelines. This review will provide an update on the most recent evidence regarding the effects of vitamin D and calcium supplements on CVD clinical outcomes, summarize ongoing vitamin D trials, and discuss the current but remarkably disparate recommendations regarding vitamin D deficiency screening and supplementation.

Background: Knowledge about mineral bone disorder (MBD) management in non-dialysis chronic kidney disease (ND-CKD) patients is scarce, although essential to identifying areas for therapeutic improvement., Methods: We prospectively evaluated current management of CKD-MBD in two visits, performed 6 months apart, in 727 prevalent ND-CKD stage 3b-5 patients from 19 nephrology clinics. Therapeutic inertia was defined as lack of treatment despite hyperphosphatemia and/or hypocalcemia, and/or hyperparathyroidism. The primary endpoint was the prevalence of achieved target for CKD-MBD parameters and related treatments (phosphate binders, vitamin D and calcium supplements). The secondary endpoint was the assessment of prevalence and clinical correlates of therapeutic inertia., Results: Over 65 % of patients did not reach parathormone (PTH) targets, while 15 and 19 % did not reach phosphate and calcium targets, respectively. The proportion of untreated patients decreased from stage 3b to 5 (at baseline, from 60 to 16 %, respectively). From baseline to the 6-month visit, the achievement of targets remained stable. Low protein diet was prescribed in 26 % of patients, phosphate binders in 17.3 % (calcium-based binders 15.5 %, aluminium binders 1.8 %), and vitamin D in 50.5 %. The overall prevalence of therapeutic inertia at the 6-month visit was 34.0 % (for hyperphosphatemia, 54.3 %). Compared to CKD stage 3, the likelihood of therapeutic inertia was 40 and 68 % lower at stage 4 and 5, respectively., Conclusions: PTH, calcium and phosphate targets were not reached in a significant proportion of patients. One-third of patients with at least one MBD parameter not-at-target remained untreated. Therapeutic inertia regarding CKD-MBD treatment may be a major barrier to optimizing the prevention and cure of CKD-MBD.

Background: Recurrent laryngeal nerve (RLN) palsy and hypoparathyroidism are serious complications in thyroid and parathyroid surgery. The extent to which incidentally detected thyroid nodules should be treated concomitantly is a matter of debate., Methods: This analysis was based on 1,065 patients who underwent consecutive surgery for primary hyperparathyroidism at a single institution. Together with the surgical strategy, histologic and follow-up examinations were documented prospectively and analyzed retrospectively regarding the occurrence and course of RLN palsy, hypoparathyroidism, and thyroid carcinoma., Results: Altogether, RLN palsy occurred for 38 patients (3.6 %) and proved to be permanent for 1 patient (0.1 %). Postoperative calcium substitution was necessary for 191 patients (17.9 %), with 3 patients showing permanent hypoparathyroidism (0.3 %). Procedures other than open minimally invasive exploration were accompanied by a significantly increased risk for temporary RLN paresis (odds ratio [OR], 6.136) and temporary hypoparathyroidism (OR 3.306). Concomitant thyroid surgery was performed for 502 patients (47.1 %). Compared with open minimally invasive parathyroid exploration, patients undergoing unilateral exploration and hemithyroidectomy (OR 5.827) or bilateral neck exploration (BNE) and thyroidectomy (OR 8.047) had a significantly increased risk for RLN paresis. Patients administered BNE with hemithyroidectomy (OR 2.380) or thyroidectomy (OR 7.233) had a significantly increased risk for hypoparathyroidism. Thyroid malignancy was incidentally detected in 86 patients (8.1 %)., Conclusion: Patients undergoing concomitant thyroid procedures have a significantly higher risk for temporary RLN palsy and hypoparathyroidism. However, the high rate of incidentally detected thyroid carcinoma in an iodine-replete endemic goiter area indicates hemithyroidectomy in the presence of thyroid nodules incidentally identified in preoperative ultrasounds.

Osteomalacia is a rare disorder of bone metabolism leading to reduced bone mineralization. Underlying vitamin D deficiency and a disturbed phosphate metabolism (so-called hypophosphatemic osteomalacia) can cause the disease. Leading symptoms are dull localized or generalized bone pain, muscle weakness and cramps as well as increased incidence of falls. Rheumatic diseases, such as polymyalgia rheumatica, rheumatoid arthritis, myositis and fibromyalgia must be considered in the differential diagnosis. Alkaline phosphatase (AP) is typically elevated in osteomalacia while serum phosphate and/or 25-OH vitamin D3 levels are reduced. The diagnosis of osteomalacia can be confirmed by an iliac crest bone biopsy. Histological correlate is reduced or deficient mineralization of the newly synthesized extracellular matrix. Treatment strategies comprise supplementation of vitamin D and calcium and for patients with intestinal malabsorption syndromes vitamin D and calcium are also given parenterally. In renal phosphate wasting syndromes substitution of phosphate is the treatment of choice, except for tumor-induced osteomalacia when removal of the tumor leads to a cure in most cases.

Hypoparathyroidism is a disorder characterized by hypocalcemia, deficient PTH, and abnormal bone remodeling. Standard treatment of hypoparathyroidism consists of oral calcium and vitamin D supplementation. However, maintaining serum calcium levels can be a challenge. In addition, concerns exist regarding hypercalciuria and ectopic calcifications that can be associated with such treatment. Hypoparathyroidism is the only classic endocrine deficiency disease for which the missing hormone, PTH, is not yet an approved treatment. This review focuses on the use of PTH in the treatment of hypoparathyroidism, in the form of teriparatide [PTH(1-34)] and the full-length molecule, PTH(1-84). Studies in hypoparathyroid subjects demonstrate that PTH(1-34) and PTH(1-84) lower or abolish supplemental calcium and vitamin D requirements as well as increase markers of bone turnover. Densitometric and histomorphometric studies in some subjects treated with PTH(1- 34) and PTH(1-84) show an improvement in bone-remodeling dynamics and return of bone metabolism toward normal levels. Given the chronic nature of hypoparathyroidism, and the expectation that PTH will be used for extended periods of time in hypoparathyroidism, further studies are needed to determine the long-term safety of PTH therapy in this population.

Background: American College of Rheumatology guidelines recommend that patients taking glucocorticoids also take calcium and vitamin D supplements, regardless of the dose or intended duration of glucocorticoid use, to decrease their risk of glucocorticoid-induced osteopenia or osteoporosis (GIOP)., Objective: To increase the number of prescriptions made for calcium and vitamin D in patients who receive a prescription for glucocorticoids using an automated, computerized order set., Design: Pre-post test design., Patients: A total of 1,041 outpatients receiving care at a single VA medical center. INTERVENTION/MAIN MEASURES: We developed an automated order set in which calcium and vitamin D were automatically co-ordered with glucocorticoid prescriptions of at least 2-week duration. We tested the impact of the order set by comparing the number of calcium and vitamin D prescriptions in patients taking glucocorticoids during a 12-month period before (T1) and after (T2) implementation. The automated order set could be modified by the treating physician, and it was not generated for patients with hypercalcemia., Key Results: A total of 535 patients during T1 and 506 patients during T2 had a glucocorticoid prescription of at least 2-week duration. The percent of co-prescriptions for calcium increased from 37 to 49% and vitamin D from 38 to 53% (both p < 0.0001) after the new automated order set was implemented., Conclusions: Implementation of an automatic prescription for calcium and vitamin D supplementation modestly increases the number of patients on glucocorticoids who are prescribed calcium and vitamin D supplementation.

Rheumatoid arthritis (RA) is a bone-destructive disease that is a serious risk factor for the development of osteoporosis, which is defined by a loss in bone quality and an increased fracture risk. The proinflammatory cytokines tumor necrosis factor-α (TNFα), interleukin-6 (IL-6) and IL-17, in particular, contribute to local and systemic bone loss in RA. While effectively reducing inflammation, glucocorticoids add to the fracture risk. Therefore, an adequate supply of calcium and vitamin D is essential. For many patients with RA, bone density measurements are recommended.

Introduction: Serum concentrations of potassium (K) and calcium (Ca) influence ionic currents and play an important role in the duration of ventricular action potential. Further, the influence of alkalosis in reducing ionized calcium has been well known for a long time. The aim of this study was to assess the effects of different dialysate electrolytes and bicarbonate concentrations on changes of QTc interval in patients on chronic hemodialysis., Methods: The study hemodialysis sessions were performed in 22 patients, with different electrolyte and bicarbonate concentrations in dialysate. Tested dialysate concentrations were K of 2 and 3 mmol/L; Ca 1.25, 1.5 and 1.75 mmol/L; and bicarbonate 30 and 34 mmol/L. An electrocardiogram (ECG) was recorded 1 hour before, at the end and every hour for 4 hours after each study dialysis session. QTc interval was measured from the beginning of the QRS complex to the end of a T wave on a 12-lead ECG. Blood was collected and K, total Ca, ionic Ca and pH evaluated., Results: At the end of the study hemodialysis session with dialysate containing low K (2 mmol/L), low Ca (1.25 mmol/L) and high bicarbonate concentration (34 mmol), mean QTc interval was significantly prolonged compared with that recorded with dialysate containing high K (3 mmol/L), high Ca (1.75 mmol/L) and bicarbonate (30 mmol) (40 ± 10 milliseconds vs. 2 ± 2 milliseconds; p<0.01). Dialysate with low concentration of low Ca, K and high concentration of bicarbonate was an independent predictor of QTc; the combination of low Ca and K and high bicarbonate strongly increased the risk of prolonged QTc interval., Conclusion: The present pilot study shows that changes in QTc interval during hemodialysis depend on both electrolyte and bicarbonate concentrations in dialysate.

In a cross-sectional study the prevalence of osteoporosis and osteopenia in patients with rheumatoid arthritis (ORA study) was investigated. Additionally, patients, their family doctors and rheumatologists were surveyed on their awareness of osteoporosis in RA, prevention, diagnosis, treatment and use of guidelines.In the years 2005 and 2006 a total of 532 patients with RA (98 men, 434 women) aged 23-87 years were consecutively recruited from 9 German centers for rheumatology. Clinical examination included a detailed documentation of osteoporosis medication. Dual-energy X-ray absorptiometry (DXA) was used to measure bone mineral density (BMD) at the lumbar spine and neck of the femur. Questionnaires on osteoporosis were sent to 119 family doctors (87 men, 32 women) and 44 rheumatologists (30 men, 14 women).The survey showed that rheumatologists had a higher awareness of osteoporosis in RA and compared to family doctors they estimated a higher frequency and tested RA patients more often for osteoporosis. In line with osteoporosis guidelines rheumatologists and family doctors saw an indication for densitometry in RA patients on steroid therapy and/or low intensity trauma fractures. In contrast to the 2006 recommendations of osteoporosis guidelines 50% of family doctors and rheumatologists preferred bisphosphonate off-label-therapy for premeopausal women with RA and comorbid glucocorticoid-induced osteoporosis. On the other hand 50% of premenopausal RA patients with osteoporosis did not receive any osteoporosis medication.The survey revealed a high degree of guideline compliance in diagnosing osteoporosis in RA but deficits were observed in the administration of osteoporosis medication, especially in premenopausal women.

Background and Aims: Given the high risk of subsequent fracture among elderly persons with fracture, it is important to initiate secondary treatment for osteoporosis. Acute rehabilitation centers may offer a unique opportunity to introduce treatment. Therefore, we evaluated willingness-to-participate and compliance with evidence-based interventions for the secondary prevention of osteoporotic fracture in a non-randomized study conducted in the acute rehabilitation setting. We also described differences in baseline characteristics between study participants and non-participants., Methods: All consecutive, community dwelling admissions to an acute rehabilitation unit (Boston, MA) with the diagnosis of fracture were screened for enrollment. Eligible subjects were offered a free, 6-month supply of alendronate/cholecalciferol (70 mg/2800 IU weekly), calcium and vitamin D supplements, and fall prevention strategies. Six-month compliance (> or =75% consumption of medication or supplement) with the interventions was determined at a home visit., Results: Among 62 eligible subjects, 25 agreed to participate. Non-participants were older than participants (86 vs 80 yrs, p<0.01). There was no significant difference between other characteristics of participants and non-participants including sex, weight, type of fracture, cognitive status, and functional status. The most common reason for non-participation was reluctance to take another medication. Among participants, only 52% were compliant with alendronate and 58% were compliant with calcium and vitamin D supplementation at 6 months., Conclusions: Willingness- to-participate and compliance with secondary prevention strategies for osteoporosis was low in the acute rehabilitation setting, even when medications were provided free of cost. Educating individuals with fracture and their families on the consequences and treatment of osteoporosis may help to decrease the risk of sustaining a second fracture by accepting secondary preventive measures.

Background and Aims: Insufficient vitamin D status, commonly found in older people, has been associated with muscle weakness which, in old age, impairs mobility and is a risk factor for falling. In a randomized, double-blind placebo-controlled trial, we tested the hypothesis that vitamin D + calcium supplementation improves muscle strength and mobility, compared with calcium mono-therapy in vitamin D-insufficient female geriatric patients., Methods: Seventy female geriatric patients >65 years of age with serum 25-hydroxyvitamin D3 (25OHD) concentrations between 20 and 50 nmol/L, visiting an outpatient geriatric department, were included. Participants received either cholecalciferol 400 IU/day + calcium 500 mg/day (D/Cal group) or a placebo + calcium 500 mg/day (Plac/Cal group) for 6 months. At baseline and 6 months, muscle strength, power and functional mobility were tested., Results: At baseline, 25OHD was significantly (p<0.05) associated with knee extension strength (r=0.42), handgrip strength (r=0.28), leg extension power (r=0.34), Timed Get Up and Go (r=-0.31) and Modified Cooper test (r=0.44). At 6 months, a significant difference in 25OHD (77.2 vs 41.6 nmol/L, p<0.001) and 1,25OHD was found between the two groups. Significantly improving vitamin D status in the D/Cal group compared with the Plac/Cal group did not result in a significant difference in strength or functional mobility between the two groups., Conclusions: Daily 400 IU vitamin D + 500 mg calcium supplementation is not enough to significantly improve strength or mobility in vitamin D-insufficient female geriatric patients.

Background and Aims: Hypovitaminosis D and K due to malnutrition or sunlight deprivation, compensatory hyperparathyroidism, increased bone resorption, low bone mineral density (BMD), and an increased risk of falls may contribute to an increased risk of hip fractures in patients with Alzheimer's disease. The purpose of the present study was to clarify the efficacy of interventions against hip fractures in patients with Alzheimer's disease., Methods: With respect to randomized controlled trials (RCTs) regarding Alzheimer's disease and hip fractures, the literature was searched with PubMed., Results: Three RCTs were identified, and the relative risk (RR) and 95% confidence interval (CI) were calculated for individual RCTs. Exposure to sunlight with calcium supplementation, menatetrenone (vitamin K2) plus calcium and vitamin D supplementation, and risedronate plus calcium and vitamin D supplementation improved hypovitaminosis D and hyperparathyroidism, contributing to a reduction in bone resorption. Risedronate itself strongly decreased bone resorption. Menatetrenone also decreased the serum level of undercarboxylated osteocalcin. The three interventions increased metacarpal BMD and reduced the incidence of hip fractures. The respective RRs (95% CI) were 0.22 (0.049-0.999), 0.13 (0.031-0.554), and 0.26 (0.100- 0.690)., Conclusions: The present study clarified the efficacy of three interventions, including exposure to sunlight, menatetrenone, and risedronate with calcium and/or vitamin D supplementation against hip fractures in patients with Alzheimer's disease.

Over one billion humans have insufficient circulating levels of vitamin D, and dietary insufficiency of calcium is common in developing countries. Worldwide, nutritional rickets is considered to be the most common non-communicable disease of children. Rickets can be due either to primary deficiencies of vitamin D or calcium or to combined deficiencies of both elements. Vitamin D deficiency is also increasingly linked to non-skeletal complications. Even without laboratory and radiologic resources, the diagnosis of rickets is considered clinically when a child presents with limb deformities and has beaded ribs and widened wrists and ankles. Prevention is possible through increased sun exposure and dietary enhancement. Treatment of nutritional rickets involves provision of adequate vitamin D and calcium. Further research is needed to elucidate the precise epidemiology of vitamin D and calcium deficiencies in developing countries, to determine the roles of additional pathologic factors contributing to the development and morbidity of rickets, to improve affordable and feasible means of diagnosing rickets in resource-limited areas, to better target at-risk populations for preventive interventions, to identify accurate dosing and delivery of therapeutic interventions, and to evaluate the long-term consequences of vitamin D and calcium deficiencies in childhood.

A 68 year old woman with a history of diabetes mellitus presented to the emergency department after experiencing several days of nausea and vomiting. Recorded vital signs included: blood pressure 98/32 mm Hg, heart rate 69 bpm, "normal" respirations, and no fever. Her initial ECG revealed peaked T waves and regular rhythm with no visible P waves. Initial serum electrolytes were notable for a potassium level of 7.7 mmol/L, and a creatinine level of 9.6 mg/dL (849 micromol/L). She was unable to provide a list of her current medications or other medical history. There was no old chart immediately available for comparison.

Transient osteoporosis of the hip is a rare clinical disorder of unknown etiology, characterized by hip pain and functional disability that resolves spontaneously in 6-24 months. Despite a benign prognosis, the long clinical course causes prolonged disability. We report on a case of transient osteoporosis of the hip during pregnancy that was rapidly resolved with the use of calcitonin. An accurate diagnosis was made 2 months after the onset of symptoms (4 weeks postpartum) based on findings in the form of bone marrow edema of the right hip by magnetic resonance imaging. The patient received calcitonin for 8 weeks and the beneficial effect was observed after 3 weeks of therapy with full resolution of symptoms after 8 weeks of therapy (4 months after onset of symptoms). We suggest that the use of calcitonin may be considered as a therapeutic intervention to shorten the disease duration.

Objective: This investigation evaluated the effectiveness of calcium and magnesium in treating oral hydrofluoric acid (HF) poisoning., Methods: The controlled laboratory investigation used anesthetized pigs. Subjects received HF via NG tube, titrated to abolish electrocardiographic abnormalities. The untreated group received saline infusion. The treatment group received serial injections of calcium chloride (CaCl2) and magnesium chloride (MgCl2). A third group received oral infusions of Calcium fluoride (CaF2). We measured heart rate, QRS interval, pH, bicarbonate, calcium, magnesium, and potassium. The Wilcoxon Rank Sum test was used to compare intra- and inter-subject differences., Results: Fatality occurred in all pigs receiving HF. Compared to the untreated group, trends for the treatment group were toward a larger amount of HF to produce fatality (83.1 +/- 17.5 grams vs. 37.7 +/- 16.1 grams, p = 0.08), to cause QRS prolongation (72.5 +/- 25.8vs. 33.8 +/- 14.9 grams, p = 0.08), and to lower potassium at mortality (4.9 +/- 0.7 vs. 8.7 +/- 2.7 mEq/L, p = 0.08). No major changes in calcium (-1.0 +/- 0.7 mEq/L) or magnesium (0.4 +/- 0.6 mEq/L) occurred in the untreated group. Tachycardia developed in all pigs and ventricular arrhythmias occurred in 2 of 3 pigs of both groups [CaF2 administration caused no QRS prolongation or ventricular arrhythmias and had no effect on laboratory parameters]., Conclusion: CaCl2 and MgCl2 replacement delayed but did not prevent fatality and QRS prolongation. Although this result suggests Ca++ and Mg++ may be beneficial in the treatment of systemic HF toxicity, factors other than hypocalcemia and hypomagnesemia play a role in toxicity.

Background: Guidelines exist for treatment of low bone mineral density (BMD). Little is known about patient characteristics associated with use of treatment., Objectives: To determine patient-related correlates of medication use following screening dual x-ray absorptiometry (DXA) of older adults., Design: Secondary analysis of a prospective cohort study., Setting: Pittsburgh, PA and Memphis, TN., Participants: Community-dwelling women between the ages 70 and 79 years enrolled in the Health, Aging, and Body Composition (Health ABC) Study., Measurements: Risk factors for fracture and BMD of the hip were assessed at baseline. Patients and their community physicians were supplied the results of the DXA scan. Prescription and over-the-counter medication use was collected at annual exams for 2 years., Results: Of 1,584 women enrolled in Health ABC, 378 had an indication for antifracture therapy and were not receiving such treatment at baseline. By the second annual follow-up examination, prescription antiresorptive medication was reported in 49 (13.0%), whereas 65 (17.2%) received calcium and/or vitamin D supplementation. In adjusted models, the strongest predictor for use of any antifracture medicine was presence of osteoporosis [vs osteopenia, odds ratio (OR), 2.9 (1.7 to 4.7)], white race [OR, 2.6 (1.5 to 4.8)], and receipt of the flu shot [OR, 2.2 (1.3 to 3.8)]. Neither a history of falls nor prior fracture was associated with use of antifracture medications., Conclusion: Even when physicians of study participants were provided with DXA scan results, 70% of older high-functioning women with an indication for therapy did not start or remain on an antifracture therapy. Substantial room for improvement exists in fracture prevention following a diagnosis of low BMD-especially among women with a history of falls, prior fractures, and among black women.

Objective: To study the pattern of use of medicines that may contribute to, or protect against, falls and fractures in the setting of a UK residential home population, and to compare the results with a similar study conducted in 2001., Setting and Method: A cross-sectional survey was conducted in 2003 in 18 residential homes. A trained community pharmacist visited the homes to retrieve information about use of medicines whilst demographic details were provided by the residential home staff., Main Outcome Measure: The proportion of patients who were prescribed medicines with a potential positive benefit in preventing fractures, and medicines that may cause elderly people to fall., Results: The study population consisted of 581 residents. Compared to the 2001 study, the use of both calcium and vitamin D had increased significantly (8.3% versus 2.1%). Although, the overall prescribing of psychotropics in 2003 was relatively low, there was a trend for increased prescribing of these medicines which have been identified as risk factors for falling., Conclusion: In a residential home setting in the UK, the use of psychotropic drugs is not uncommon, whereas there is limited use of drugs that have the potential for preventing morbidity associated with falls.

In contrast to postmenopausal osteoporosis, the overriding objective in senior citizens older than 75 years is to avoid fractures of the hip, which are associated with a high mortality rate. Bone density measurement obtained at the neck of the femur using DXA provides reliable data on the risk of an individual patient of sustaining a fracture close to the hip joint. A physical examination can help to assess the patient's risk of falling, while diagnostic laboratory studies can help to exclude secondary osteoporosis. As a preventive measure, physical activity can increase bone density also in old age. Calcium and vitamin D improve muscular strength and coordination, and thus also may be helpful in preventing falls. In manifest osteoporosis, risedronate and alendronate reduce the risk of fractures close to the hip and of vertebrae by 50%. In addition, raloxifene can be employed to prevent vertebral fractures.

A successful prevention strategy for fractures in the elderly should not be limited to an improvement in bone mineral density. Equally important is the prevention of falls. Thus, 90% of fractures in the elderly are associated with a fall and 30% of all ambulatory, and 50% of institutionalized elderly age 65 years and older fall at least once a year. Fall incidence increases 10% per decade thereafter. According to recent studies, vitamin D and calcium supplementation may be a promising treatment strategy targeting both bone mineral density, as well as muscle strength and the risk of falling. The protective effect of vitamin D on fractures has been attributed to the established moderate benefit of vitamin D on bone mineral density. However, an alternative explanation might be that vitamin D affects factors directly related to muscle strength, thus, reducing fracture risk through improved function and fall prevention, in addition to its benefits on calcium homeostasis.

The aim of this study was to analyse the heterogeneity of bone mineral density (BMD) reduction across measurement sites in female systemic lupus erythematosus (SLE) patients on glucocorticoid (CS) treatment. The study population consisted of two subgroups: 32 women at a mean (SD) age of 43.2 (12.0) years, SLE duration of 13.4 (6.2) years, treated with a mean cumulative prednisone dose of 34.4 g; and 16 women at a mean age of 36.1 (9.0) years, SLE duration of 3.2 (2.0) years, never treated with glucocorticoids (control group). The participants underwent a standardised interview, medical record review, blood sampling and BMD examination of the lumbar spine, femoral neck and distal forearm by dual-energy X-ray absorptiometry. CS-treated participants were supplemented with daily calcium (1200 mg) and vitamin D (500 UI). During the study mean daily glucocorticoid dose was 10 mg prednisone equivalent. The controls did not receive either corticosteroids or calcium and vitamin D. BMD and laboratory parameters were re-examined at the end of the second year. At baseline 22 (68.7%) of the CS-treated participants had osteoporosis at least at one major site, compared to 18.8% of the controls. The BMD reduction was proportional to the trabecular bone content at the specific measurement site. At baseline mean T scores in the CS-treated group were the highest at the forearm (-1.03 +/- 1.13), followed by the hip (-1.32 +/- 1.26), AP spine (-1.87 +/- 1.46) and lateral spine (-2.90 +/- 1.50). At follow-up lateral spine bone loss was 5.54% per year, the total hip and the forearm lost 3.59% and 0.33%, respectively, compared to annual losses of 1.02% (AP spine), 1.30% (lateral spine), 0.83% (total hip) and 0.11% (forearm) in the control group. The heterogeneity of BMD reduction in our SLE population emphasises the need for the targeted use of bone densitometry in steroid-treated patients. Attention should be paid to trabecular-rich sites, and fracture risk should be specifically determined.