The incidence of hypocalcemia and bone mineral density (BMD) changes in end-stage renal disease (ESRD) patients on denosumab remains unclear. We performed this meta-analysis to assess the incidence of denosumab-associated hypocalcemia and effects of denosumab on BMD in ESRD patients. A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through November 2017 to identify studies evaluating incidence of denosumab-associated hypocalcemia and changes in serum calcium, phosphate, alkaline phosphatase (ALP), parathyroid hormone (PTH), and BMD from baseline to post-treatment course of denosumab in ESRD patients. Study results were pooled and analyzed using a random-effect model. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017081074). Six observational studies with a total of 84 ESRD patients were enrolled. The pooled estimated incidence of hypocalcemia during denosumab treatment was 42% (95% CI 29–55%, I2 = 0%). Hypocalcemia occurred approximately 7 to 20 days after the first dose and reached nadir of low calcium levels in the first 2 weeks up to 2 months. However, there were no significant changes in serum calcium or phosphate from baseline to post-treatment course (≥ 3 months after treatment) with mean differences [MDs] of 0.20 mg/dL (95% CI, − 0.30 to 0.69 mg/dL) and − 0.10 mg/dL (95% CI, − 0.70 to 0.49 mg/dL). There were significant reductions in ALP and PTH levels with standardized mean differences (SMDs) of − 0.65 (95% CI − 1.13 to − 0.16) and − 1.89 (95% CI − 3.44 to − 0.34), respectively. There were significant increases in T-scores with MDs of 0.39 (95% CI 0.10 to 0.69) and 0.79 (95% CI 0.60 to 0.98) for lumbar spine and femoral neck, respectively. Our study demonstrates the estimated incidence of denosumab-associated hypocalcemia in dialysis patients of 42%. From baseline to post-treatment course, although there are no differences in serum calcium and phosphate, our findings suggest significant reductions in ALP and PTH and a significant increase in BMD. Currently, denosumab should not be considered as the treatment of choice in ESRD patients until more safety and efficacy data are available.

The purpose of this randomized controlled trial was to investigate temporal skeletal responses to short-term high intensity physical activity. Twenty-eight normal active females [age: 20.7 +/- 2.1 yr (mean +/- SD)] were randomized into exercise (EX, n = 15) or control (CN, n = 13) groups. The exercise group trained 6 days/wk for 6 wk, which consisted of maximal isokinetic knee flexion/extension 3 days/wk, combined with 3 days/wk running. The purpose was to expose the tibiae to a period of abruptly increased loading forces. Tibial bending stiffness (EIMRTA), and serum concentrations of biochemical markers of bone formation [osteocalcin (OC)], and bone resorption [n-telopeptide of type I collagen (NTx)] were measured at baseline, 2 wks, 4 wks, and 6 wks. Isokinetic concentric knee extension/flexion peak torque, as well as total body and site-specific bone mineral density (BMD) were measured at baseline and 6 wk. After training, the exercise group significantly increased (p < 0.05) isokinetic concentric peak torque for the dominant (13.6%) and non-dominant (5.7%) quadriceps, as well as dominant (7.7%) and non-dominant (9.5%) hamstrings, compared to the controls. No differences for total body or site-specific BMD were noted. A two-way multivariate repeated measures ANOVA revealed no timeâ ¢group interactions for composite tibial bending stiffness [(EIMRTA); p = 0.57] or the biochemical markers of bone turnover [(OC and NTx); p = 0.15] across the four sampling periods. While there were no main effects for group, a trend for time (p = 0.051) for composite EIMRTA was observed. The exercise group demonstrated a 20% increase in EIMRTA from baseline (74.8 +/- 22.3 Nm2) to 6 wk (89.8 +/- 24 Nm2), compared to controls who demonstrated a 4% increase (Baseline 86.5 +/- 23.8 Nm2; 6 wk 90 +/- 23.7 Nm2). Significant group differences (p = 0.05) were noted for OC, but not NTx. Differences (p < 0.05) for OC were observed at baseline [13.2 +/- 2.4 ng/ml (CN), 15.6 +/- 2.7 ng/ml (EX)], and follow-up ANCOVA revealed no differences for subsequent sampling periods. Main effects for time were found for OC and NTx (p < 0.001). Main effects for time in OC were attributable to changes in the exercise group (p < 0.01) and NTx (p < 0.01), but not the control group. / Ph. D.

Background: Lithium is the most effective long-term treatment for bipolar disease. It has, however,been associated with hypercalcemia and hyperparathyroidism. The aim of the study is to research howlithium associated hyperparathyroidism(LHPT)affects bone mineral density. Method: A sub-analysis was performed on an ongoing randomized prospective study evaluating the operation results from parathyroidectomy versus watchful waiting in 22patients with LHPT. The patients were followed-up for 2 years and their blood samples, bone mineral density (BMD) and FRAX assessment were analysed. The data from LHPT patients was also compared to a separate group of patients with primary hyperparathyroidism (PHPT) corresponding in age.Results: In comparing LHPT patients with PHPT apparent differences in the biochemical profile were detected, including elevated values of ionized Ca in PHPT (p=0.001), lower excretion of 24h urinary calcium in LHPT (p=0.003) and significantly higher values of PTH excretion in PHPT. LHPT showed tendencies to having better BMD (p=0.176). At 2-year follow-up of 8 LHPT patients, biochemicalvalues improved, suggesting cure, including lower risks of skeletal fractures. Discussion: The biochemical features in LHPT are distinctive from PHPT. However, each case is unique, and thebiochemicalvariety issimilar to PHPT. Confounding factors include age, sex, renal function and stability of the bipolar condition. Conclusions:The present study illustratesthat LHPT differs biochemically from PHPT. In comparison to PHPT, LHPT patients tend to have reduced BMD and the present study could not confirm the previous postulation that lithium could be protective of the skeleton. In conclusion, casesof LHPT should be assessed individually, since the clinical course is diverse. In patients risking fracture, parathyroidectomy should be considered.

Background: Lithium is the most effective long-term treatment for bipolar disease. It has, however,been associated with hypercalcemia and hyperparathyroidism. The aim of the study is to research howlithium associated hyperparathyroidism(LHPT)affects bone mineral density. Method: A sub-analysis was performed on an ongoing randomized prospective study evaluating the operation results from parathyroidectomy versus watchful waiting in 22patients with LHPT. The patients were followed-up for 2 years and their blood samples, bone mineral density (BMD) and FRAX assessment were analysed. The data from LHPT patients was also compared to a separate group of patients with primary hyperparathyroidism (PHPT) corresponding in age.Results: In comparing LHPT patients with PHPT apparent differences in the biochemical profile were detected, including elevated values of ionized Ca in PHPT (p=0.001), lower excretion of 24h urinary calcium in LHPT (p=0.003) and significantly higher values of PTH excretion in PHPT. LHPT showed tendencies to having better BMD (p=0.176). At 2-year follow-up of 8 LHPT patients, biochemicalvalues improved, suggesting cure, including lower risks of skeletal fractures. Discussion: The biochemical features in LHPT are distinctive from PHPT. However, each case is unique, and thebiochemicalvariety issimilar to PHPT. Confounding factors include age, sex, renal function and stability of the bipolar condition. Conclusions:The present study illustratesthat LHPT differs biochemically from PHPT. In comparison to PHPT, LHPT patients tend to have reduced BMD and the present study could not confirm the previous postulation that lithium could be protective of the skeleton. In conclusion, casesof LHPT should be assessed individually, since the clinical course is diverse. In patients risking fracture, parathyroidectomy should be considered.

Final publication is avilable at http://www.sciencedirect.com/science/article/pii/S0954611115300172 / 京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19577号 / 医博第4084号 / 新制||医||1013(附属図書館) / 32613 / 京都大学大学院医学研究科医学専攻 / (主査)教授 伊達 洋至, 教授 平家 俊男, 教授 松田 秀一 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19603号 / 医博第4110号 / 新制||医||1014(附属図書館) / 32639 / 京都大学大学院医学研究科医学専攻 / (主査)教授 中山 健夫, 教授 富樫 かおり, 教授 松田 秀一 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

Bakgrund: Osteoporos har under de senaste decennierna utvecklats till en av de stora folksjukdomarna. I Sverige drabbas cirka 70 000 människor av osteoporosrelaterade frakturer varje år och av dessa är det främst kvinnor som drabbas. Risken för att en svensk kvinna någon gång under sin livstid skall drabbas av en osteoporosrelaterad fraktur är 50 %. Hur snabbt en kvinna förlorar benmassan samt hur stor benmassa hon har från början är avgörande för om hon kommer att drabbas av osteoporos och därför är prevention i ett tidigt skede viktigt. Syfte: Syftet med litteraturstudien var att belysa preventiva åtgärder för premenopausala kvinnor som kan förebygga primär osteoporos. Metod: Metoden var en litteraturstudie bestående av tio vetenskapliga artiklar baserade på kvantitativ forskning. Resultat: Resultaten visade att ett dagligt intag av gröna och gula grönsaker har en positiv effekt på benmassan. Ett års tillskott av antingen vitamin D, kalcium eller MMN-kalcium ökade Bone Mineral Density (BMD) hos kvinnor med underskott av D-vitamin. Fysisk aktivitet i form av tolv månaders high impact exercise ökade benmassan i loaded bones i nedre extremiteterna och i övre ländryggen (L1). Elitidrottare hade högre bentäthet jämfört med icke atleter och elitidrottare som utövade high impact exercise hade högre BMD än de som utövade medium impact och low impact exercie. Bentätheten ökade inte mer vid fysisk aktivitet och ett samtidigt intag av kalcium. Bentäthetsmätning och undervisning om osteoporos var effektivt för förändring av livsstil. Rökning och passiv rökning har en negativ inverkan på benmassan då de som rökte eller var utsatta för passiv rökning hade ett lägre BMD. Slutsats: Slutsatsen som drogs var att dessa resultat belyser viktiga faktorer som sjuksköterskan kan använda i det preventiva arbetet av primär osteoporos hos premenopausala kvinnor. Med kunskap från litteraturstudien kan sjuksköterskan undervisa patienter om åtgärder som är relativt enkla att ta till. Det krävs dock mer forskning för att stärka bevisen för de preventiva åtgärderna. / Background: Osteoporosis has during the last decades developed into one of the bigger common diseases. Each year around 70 000 people in Sweden suffers from fractures related to osteoporosis, with women being the majority. There is a 50 % risk that a swedish woman at some point during her lifetime will suffer from an osteoporosis related fracture. The rate at which a woman loses her bone density and how dense it initially was, determines whether she will get osteoporosis and early prevention is therefore imperative. Aim: The aim of this study was to highlight preventive measures for pre-menopausal women and prevent primary osteoporosis. Method: The method used was a literature study consisting of ten scientific articles based on quantitative research. Result: The result showed that a daily intake of green and yellow vegetables has a positive affect on density. One year of supplements with either vitamin D, calcium or MMN- calcium increased the Bone Mineral Density (BMD) in women with a lack of vitamin D. Physical activity such as twelve month of high impact exercise increased the bone density in loaded bones in the lower extremities and in upper lumbar spine (L1). Professional athletes had a higher bone density compared with non professional athletes, and professional athletes doing high impact exercise had a higher BMD than those who practiced medium and low impact exercise. The effect of physical activity on bone density is not greater when combined with calcium intake. Measuring bone density and education regarding osteoporosis showed to be an effective way for lifestyle changes. Smoking and passive smoking has showed to have a negative effect on bone density as those who smoked or were considered passive smokers had a lower BMD. Conclusion: The conclusion of the results shows important factors needed by nurses when working to prevent primary osteoporosis in pre- menopausal women. The nurse can with the knowledge from the literature study educate patients regarding measures that are rather simple to follow. However, more research is needed to strengthen and improve the evidence regarding preventive measure.

In the United States, osteoporosis results in about 1.5 million annual fractures, costing approximately $15 billion. Calcitonin is safe and effective in slowing osteoporotic bone loss, but its effect is transient. The current studies were designed to explore the dose-dependent effects of salmon calcitonin on bone turnover in ovariectomized rats and to determine if the decrease in therapeutic effectiveness of calcitonin demonstrated over time with higher doses is due to oversuppression of bone turnover. Doses of 5, 15, & 50 IU/kg BW/day of calcitonin were compared to placebo in 12-week-old ovariectomized and sham-ovariectomized Sprague-Dawley rats for 24 weeks. The spinal bone mineral content (BMC) as measured by DXA in ovariectomized subjects receiving 5 & 15 IU/kg of calcitonin was not significantly different from sham-ovariectomized subjects, while spinal BMC of subjects receiving 50 IU/kg was significantly lower than shamovariectomized subjects (p<0.05). Femoral BMC of ovariectomized subjects was significantly lower than sham-ovariectomized subjects (p<0.05), but no significant differences were noted between treatment groups. Scanning electron microscopy (SEM) demonstrated a decrease in number and density of trabeculae and in cortical thickness when comparing femurs from ovariectomized with sham-ovariectomized subjects. SEM of subjects receiving 50 IU/kg displayed greater bone loss than other groups. No significant differences were noted between groups for levels of urinary helical peptides or serum pyridinoline [ELISA], indicators of bone resorption. Urinary calcium excretion [capillary ion electrophoresis] was significantly higher in subjects receiving 50 IU/kg of calcitonin than other ovariectomized subjects (p<0.05). Serum levels of osteocalcin [RIA], an indicator of bone formation, were significantly higher in subjects receiving 5 IU/kg of calcitonin than control subjects and those receiving 50 IU/kg (p<0.05). Production of antibodies to calcitonin [ELISA] by subjects in this study did not correlate with changes in bone turnover or bone density. The results of this study do not provide evidence higher doses of calcitonin result in oversuppression of bone turnover. However, urinary calcium excretion affected bone resorption in a reverse dose-dependent manner, suggesting the calciuric effect may be responsible for less effective outcomes seen with higher doses of calcitonin.

The postpartum period represents a high-risk period for body weight retention and obesity. Several studies have investigated the role of aerobic exercise on postpartum weight retention and other body composition outcomes; however, there has been little attention given to resistance training in postpartum women. Thus, the purpose of this four-month randomized study was to determine the effectiveness of resistance training on strength, body composition, return to pre-pregnancy weight, and bone mineral density (BMD) in postpartum women. Sixty postpartum women were randomly assigned to either a resistance training group or a comparison group. The resistance training group participated in a progressive resistance training program twice weekly for four months. The comparison group participated in a flexibility program twice weekly for four months. Strength changes were assessed for the upper body (bench press), lower body (leg press), and the core (abdominal curl-ups). Body composition, including BMD, was measured by dual energy x-ray absorptiometry. Over the four-month study, the resistance training group demonstrated a 36.7% increase in bench press, a 31.1% increase in leg press, and a 222.6% increase in abdominal curl-ups (p < 0.05). The flexibility group improved by 7.7% for bench press, 6.6% for leg press, and by 43.0% for abdominal curl-ups (p < 0.05). Group*period interactions were significant for the leg press, bench press, and abdominal curl-ups (p < 0.05). Both groups decreased in body weight, body fat percentage, and fat tissue (p < 0.05). Neither group significantly changed in lean tissue, whole body BMD, and hip BMD (p > 0.05). Group*period interactions were not significant for any body composition outcome (p > 0.05). These results suggest that a twice weekly resistance training program is superior to flexibility training to increase strength; however, resistance training may not be enough to influence body composition to a greater extent than flexibility training in postpartum women. More research is warranted.