Calcium and vitamin D supplementation maintains parathyroid hormone and improves bone density during initial military training: A randomized,double-blind,placebo controlled trial

Calcium and vitamin D are essential nutrients for bone health. Periods of activity with repetitive mechanical loading, such as military training, may result in increases in parathyroid hormone (PTH), a key regulator of Ca metabolism, and may be linked to the development of stress fractures. Previous studies indicate that consumption of a Ca and vitamin D supplement may reduce stress fracture risk in female military personnel during initial military training, but circulating markers of Ca and bone metabolism and measures of bone density and strength have not been determined. This randomized, double-blind, placebo-controlled trial sought to determine the effects of providing supplemental Ca and vitamin D (Ca + Vit D, 2000 mg and 1000 IU/d, respectively), delivered as 2 snack bars per day throughout 9 weeks of Army initial military training (or basic combat training, BCT) on PTH, vitamin D status, and measures of bone density and strength in personnel undergoing BCT, as well as independent effects of BCT on bone parameters. A total of 156 men and 87 women enrolled in Army BCT (Fort Sill, OK; 34.7°N latitude) volunteered for this study. Anthropometric, biochemical, and dietary intake data were collected pre- and post-BCT. In addition, peripheral quantitative computed tomography was utilized to assess tibia bone density and strength in a subset of volunteers (n = 46). Consumption of supplemental Ca + Vit D increased circulating ionized Ca (group-by-time, P = 0.022), maintained PTH (group-by-time, P = 0.032), and increased the osteoprotegerin:RANKL ratio (group-by-time, P = 0.006). Consistent with the biochemical markers, Ca + Vit D improved vBMD (group-by-time, P = 0.024) at the 4% site and cortical BMC (group-by-time, P = 0.028) and thickness (group-by-time, P = 0.013) at the 14% site compared to placebo. These data demonstrate the benefit of supplemental Ca and vitamin D for maintaining bone health during periods of elevated bone turnover, such as initial military training.This trial was registered with ClincialTrials.gov, NCT01617109.     

The effect of sevoflurane compared to propofol maintenance on post-surgical quality of recovery in patients undergoing an ambulatory gynecological surgery: A prospective,randomized, double-blinded,controlled, clinical trial

ObjectiveThe main objective of the current investigation was to evaluate the effect of propofol used as anesthetic maintenance compared to sevoflurane on global post-surgical quality of recovery in female patients undergoing ambulatory gynecological surgery.DesignThe study was a prospective randomized double blinded, controlled, clinical trial.InterventionsHealthy female subjects were randomized to receive propofol or sevoflurane as anesthetic maintenance.MeasurementsThe primary outcome was the Quality of Recovery 40 (QOR-40) questionnaire at 24 h after surgery. Other data collected included opioid consumption, pain scores and time to hospital discharge. P < 0.05 was used to reject the null hypothesis for the primary outcome.Main resultsNinety subjects were randomized and sixty seven completed the study. Patient's baseline characteristics and surgical factors were not different between study groups. There was not a clinically significant difference in the global QoR-40 scores between the sevoflurane and the propofol groups, median (IQR) of 175 (163 to 181) and 176 (163 to 184), respectively, P = 0.97. There was an inverse relationship (ρ = − 0.42) between the opioid consumption in PACU (IV morphine equivalents) and 24 h postoperative quality of recovery (P < 0.001) and an inverse relationship (ρ = − 0.48) between the oral opioid consumption at home (oral morphine equivalents) and 24 h postoperative quality of recovery, P < 0.001.ConclusionsOur current results do not support the use of total intravenous anesthesia as an efficacious strategy to improve global quality of recovery after ambulatory surgery. Opioid consumption in the PACU is an earlier surrogate that can be utilized to identify ambulatory patients with a high likelihood to develop poor global quality of recovery and who may benefit from more efficacious strategies to improve global quality of recovery.Trial registration: ClinicalTrial.gov; url: http://www.clinicaltrials.gov; registration identified: NCT 01755234.     

Vitamin D levels in post-menopausal Korean women with a distal radius fracture

IntroductionThe purpose of this study was to investigate serum levels of vitamin D in post-menopausal Korean women with a distal radius fracture (DRF) and to determine if there is any association between vitamin D levels and bone-related variables such as bone mineral densities (BMDs), serum parathyroid hormone (PTH) levels and several bone turnover markers.Materials and methodsThe data of 104 postmenopausal women surgically treated for a distal radius fracture (DRF group) and 107 age-matched control patients without a fracture (control group) were compared. Serum vitamin D levels (25-hydroxycholecalciferol, 25(OH)D₃) were compared between the groups with consideration of age and seasonal variations. BMDs, serum PTH and several bone turnover markers, including serum osteocalcin, C-telopeptide and urine N-telopeptide, were measured and analysed to find any association with vitamin D levels.ResultsThe mean 25(OH)D₃ level was significantly lower in the DRF group compared to the control group (p < 0.001). In particular, patients in their sixth and seventh deciles in the DRF group had significantly lower 25(OH)D₃ levels than patients in the control group (p = 0.001 and 0.013, respectively). When seasonal variation was considered, significant differences of 25(OH)D₃ levels were found between the groups in autumn and winter. Hip BMDs were significantly lower in the DRF group than in the control group, and there was a positive correlation between serum 25(OH)D₃ levels and hip BMDs. Bone turnover markers were not significantly different between the two groups, although serum PTH levels were marginally higher in the DRF group (p = 0.08).ConclusionsPost-menopausal Korean women with a DRF were found to have significantly lower serum vitamin D levels than the control group, and vitamin D levels were particularly lower in women in their sixth and seventh deciles who may be a good target group for prevention of future fractures. Future investigation should focus on determining whether vitamin D supplementation can be helpful in preventing future fractures in patients with a DRF.     

Is gabapentin effective and safe in open hysterectomy? A PRISMA compliant meta-analysis of randomized controlled trials

BackgroundPain management after open hysterectomy has been investigated for years. Owing to the effect of significant analgesic, gabapentin was often administrated for pre-emptive analgesia. However, the relationship between gabapentin and postoperative pain after open hysterectomy is still controversial. This meta-analysis was applied to assess the efficacy of pre-emptive use of gabapentin in open hysterectomy.MethodsThis meta-analysis of randomized controlled trials (RCTs) was performed to compare the use of gabapentin with placebo in open hysterectomy regarding (1) the mean difference (MD) of postoperative opioid requirements; (2) the changes of visual analogue scale (VAS) scores in two groups; and (3) incidence rate of adverse effects. Systematic searches of all related literatures was conducted using the following databases: MEDLINE, EMBASE, ClinicalTrials.gov and Web of Science. Only randomized controlled trials (RCTs) for open hysterectomy were included. The MD of postoperative opioid requirements and VAS scores, relative risk (RR) of incidence rate of adverse effects in the gabapentin group versus placebo group were extracted throughout the study.ResultsFourteen trials were included in this meta-analysis. The total opioid consumption at 24 h was a less in gabapentin group. (MD = − 11.61, 95% CI: − 16.71 to − 6.51, P = 0.00) The visual analogue scale (VAS) score at 4, 12 and 24 h were less in the gabapentin group. (MD = − 16.83, 95% CI: − 22.88 to − 10.77, P = 0.00), (MD = − 17.45, 95% CI: − 21.83 to − 13.08, P = 0.00), (MD = − 9.83, 95% CI: − 13.31 to − 6.35, P = 0.00) The incidence rate of vomiting and nausea were significantly less in gabapentin groups. (RR 0.13, 95% CI 0.45 to 0.73, P = 0.00), (RR 0.67, 95% CI 0.49 to 0.93, P = 0.02). Compared with placebo, gabapentin achieved higher patient satisfaction. (MD = 20.43, 95% CI: 12.42 to 28.44, P < 0.00).ConclusionThis meta-analysis suggested that the employment of gabapentin was efficacious in reduction of postoperative opioid consumption, VAS score and some side effects after open hysterectomy.     

The effects of beta-2 adrenergic agonist and antagonist on human bone metabolism: A randomized controlled trial

PurposeGenetic knockout or pharmacological inhibition of the beta-2 adrenergic receptor (B2AR) increased bone mass, whereas stimulation decreased bone mass in rodents. In humans, observational studies support sympathetic nervous system regulation of bone metabolism, but intervention studies are lacking. We aimed to determine the effects of a selective beta-2 adrenergic agonist and non-selective antagonist on human bone metabolism.Methods32 healthy postmenopausal women were included in a randomized controlled trial conducted in the Academic Medical Center Amsterdam. Participants were randomized to receive treatment with 17-β estradiol 2 mg/day; 17-β estradiol 2 mg/day and terbutaline 5 mg/day (selective B2AR agonist); propranolol 80 mg/day (non-selective B-AR antagonist); or no treatment during 12 weeks. Main outcome measure was the change in serum concentrations of procollagen type I N propeptide (P1NP) and C-terminal crosslinking telopeptides of collagen type I (CTx) as markers of bone formation and resorption after 12 weeks compared between the treatment groups. Data were analyzed with mixed model analysis.Results17-β estradiol decreased bone turnover compared to control (P1NP p < 0.001, CTx p = 0.003), but terbutaline combined with 17-β estradiol failed to increase bone turnover compared to 17-β estradiol alone (P1NP p = 0.135, CTx p = 0.406). Propranolol did not affect bone turnover compared to control (P1NP p = 0.709, CTx p = 0.981).ConclusionSelective beta-2 adrenergic agonists and non-selective beta-antagonists do not affect human bone turnover although we cannot exclude small changes below the detection limit of this study.     

Comparative effects of raloxifene and alendronate on fracture outcomes in postmenopausal women with low bone mass

The double-blind, randomized raloxifene alendronate comparison trial was the first study designed to compare two osteoporosis therapies head-to-head for fracture risk reduction. The original protocol planned to treat 3000 postmenopausal women with alendronate 10 mg/day (ALN) or raloxifene 60 mg/day (RLX) for 5 years, and to recruit women (50–80 years old) with a femoral neck bone mineral density (BMD) T-score between − 2.5 and − 4.0, inclusive, no prevalent vertebral fractures, and no prior bone-active agent use. The trial was stopped early, due to difficulty in finding treatment-naïve women to meet enrollment goals within the planned timeline, resulting in insufficient power to show non-inferiority between therapies in the primary endpoint (number of women with ≥ 1 new osteoporotic vertebral or nonvertebral fracture). Except for vertebral fractures, fracture analyses were based upon 1412 of the 1423 women randomized (mean age of 66 years). After 312 ± 254 days (mean ± SD), 22 women in the ALN group and 20 in the RLX group had new vertebral or nonvertebral fractures. Four women in the ALN group and none in the RLX group had moderate/severe vertebral fractures, a pre-specified endpoint (P = 0.04). Lumbar spine, femoral neck, and total hip BMD were increased from baseline at 2 years in each group (P < 0.001), with greater increases in the ALN group (each P < 0.05). Similar numbers of women in each group had ≥ 1 adverse event and discontinued due to an adverse event. The only adverse events with an incidence that differed between groups were colonoscopy, diarrhea, and nausea; each was more common with ALN treatment (each P < 0.05). One woman in each group had a venous thromboembolic event. One case of breast cancer occurred in each group. In summary, as this trial was terminated early, there was insufficient power to compare the fracture risks between alendronate and raloxifene. Safety profiles were as expected from clinical trial and post-marketing reports.Trial Registration: ClinicalTrials.gov Identifier NCT00035971.     

Vitamin D deficiency promotes growth of MCF-7 human breast cancer in a rodent model of osteosclerotic bone metastasis

IntroductionBreast cancer metastases to bone are common in advanced stage disease. We have recently demonstrated that vitamin D deficiency enhances breast cancer growth in an osteolytic mouse model of breast cancer metastasis. In this study, we examined the effects of vitamin D deficiency on tumor growth in an osteosclerotic model of intra-skeletal breast cancer in mice.MethodsThe effects of 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] on proliferation and apoptosis of MCF-7 breast cancer cells, and changes in the expression of genes within the vitamin D metabolic pathway (VDR, 1α- and 24-hydroxylase) were examined in vitro. MCF-7 breast cancer cells were injected intra-tibially into vitamin D deficient and vitamin D sufficient mice co-treated with and without osteoprotegerin (OPG). The development of tumor-related lesions was monitored via serial X-ray analysis. Tumor burden and indices of proliferation and apoptosis were determined by histology along with markers of bone turnover and serum intact PTH levels.ResultsIn vitro, MCF-7 cells expressed critical genes for vitamin D signalling and metabolism. Treatment with 1,25(OH)₂D₃ inhibited cell growth and proliferation, and increased apoptosis. In vivo, osteosclerotic lesions developed faster and were larger at endpoint in the tibiae of vitamin D deficient mice compared to vitamin D sufficient mice (1.49 ± 0.08 mm² versus 1.68 ± 0.15 mm², P < 0.05). Tumor area was increased by 55.8% in vitamin D deficient mice (0.81 ± 0.13 mm² versus 0.52 ± 0.11 mm² in vitamin D sufficient mice). OPG treatment inhibited bone turnover and caused an increase in PTH levels, while tumor burden was reduced by 90.4% in vitamin D sufficient mice and by 92.6% in vitamin D deficient mice. Tumor mitotic activity was increased in the tibiae of vitamin D deficient mice and apoptosis was decreased, consistent with faster growth.ConclusionVitamin D deficiency enhances both the growth of tumors and the tumor-induced osteosclerotic changes in the tibiae of mice following intratibial implantation of MCF-7 cells. Enhancement of tumor growth appears dependent on increased bone resorption rather than increased bone formation induced by these tumors.     

Relationship between vitamin D deficiency and bone fragility in sickle cell disease: A cohort study of 56 adults

BackgroundRecent studies suggest that patients with sickle cell disease (SCD) have profound vitamin D (VD) deficiency. Limited data exist on the effect of VD deficiency on bone fragility in these patients.ObjectivesTo assess the prevalence of VD deficiency in adults with SCD and its consequences on bone metabolism and fragility.MethodsThis prospective study included 56 SCD adult patients (mean age 29.8 ± 9.5 years), in a clinically steady state. Clinical and laboratory data were recorded. Bone mineral density (BMD) was measured using dual X-ray absorptiometry. Fracture history, BMD, avascular osteonecrosis, H-shaped vertebra and markers of mineral metabolism were compared between two groups of patients presenting very low (≤ 6 ng/mL, n = 26) (group 1) and low (> 6 ng/mL, n = 26) (group 2) 25(OH)D concentration, respectively.ResultsMedian 25(OH)D concentration was 6 ng/mL. VD deficiency (25(OH)D < 10 ng/mL) was found in 42 out of 56 patients (75%) and secondary hyperparathyroidism in 40 (71.4%). History of fracture was documented in 17 patients (30.3%), osteopenia and/or osteoporosis in 39.6% of patients. Overall, patients of group 1 were more likely to have sustained a fracture (42.8%) compared to patients of group 2 (17.8%) (p = 0.04). These patients had also lower body mass index and significantly higher parathyroid hormone, C-terminal telopeptides of type I-collagen and bone-specific alkaline phosphatase serum levels. There was no difference between group for BMD, avascular osteonecrosis history, H-shaped vertebra, and disease severity markers.ConclusionThis study suggests that VD deficiency is a key feature in SCD-bone disease. It is highly prevalent and associated with hyperparathyroidism, bone resorption markers, and history of fracture. The optimal supplementation regimen remains to be determined.     

Fat suppression at three-dimensional T1-weighted MR imaging of the hands: Dixon method versus CHESS technique

Purpose

To compare the effectiveness of fat suppression and the image quality of the Dixon method with those of the chemical shift-selective (CHESS) technique in hands of normal subjects at non-enhanced three-dimensional (3D) T1-weighted MR imaging.

Early diet and peak bone mass: 20 year follow-up of a randomized trial of early diet in infants born preterm

BackgroundPreterm infants are at risk of metabolic bone disease due to inadequate mineral intake with unknown consequences for later bone health.ObjectiveTo test the hypotheses that (1) early diet programs peak bone mass and bone turnover; (2) human milk has a beneficial effect on these outcomes; (3) preterm subjects have reduced peak bone mass compared to population reference data.Design20 year follow-up of 202 subjects (43% male; 24% of survivors) who were born preterm and randomized to: (i) preterm formula versus banked breast milk or (ii) preterm versus term formula; as sole diet or supplement to maternal milk. Outcome measures were (i) anthropometry; (ii) hip, lumbar spine (LS) and whole body (WB) bone mineral content (BMC) and bone area (BA) measured using DXA; (iii) bone turnover markers.ResultsInfant dietary randomization group did not influence peak bone mass or turnover. The proportion of human milk in the diet was significantly positively associated with WBBA and BMC. Subjects receiving > 90% human milk had significantly higher WBBA (by 3.5%, p = 0.01) and BMC (by 4.8%, p = 0.03) than those receiving < 10%. Compared to population data, subjects had significantly lower height SDS (? 0.41 (SD 1.05)), higher BMI SDS (0.31 (1.33)) and lower LSBMD SDS (? 0.29 (1.16)); height and bone mass deficits were greatest in those born SGA with birthweight < 1250 g (height SDS ? 0.81 (0.95), LSBMD SDS ? 0.61 (1.3)).ConclusionInfant dietary randomization group did not affect peak bone mass or turnover suggesting the observed reduced final height and LS bone mass, most marked in growth restricted subjects with the lowest birthweight, may not be related to sub-optimal early nutrition. The higher WB bone mass associated with human milk intake, despite its low nutrient content, may reflect non-nutritive factors in breast milk. These findings may have implications for later osteoporosis risk and require further investigation.     

Hip fracture type: Important role of parathyroid hormone (PTH) response to hypovitaminosis D

ObjectiveTo investigate whether clinical and laboratory characteristics, including serum 25-hydroxyvitamin D (25(OH) D), PTH and parameters of mineral and bone metabolism, differ by hip fracture (HF) type.Patients and methodsWe studied prospectively 761 consecutively admitted older patients (mean age 82.3 + 8.8(SD) years; 74.9% women) with low trauma non-pathological HF. A detailed clinical examination was performed, haematologic, renal, liver and thyroid function tests, serum 25(OH)D, PTH, calcium, phosphate, magnesium, C-reactive protein (CRP) and cardiac troponin I (cTnI) measured. In a subset of 294 patients' markers of bone formation (serum osteocalcin, OC; bone specific alkaline phosphatase, BAP) and bone resorption (urinary deoxypyridinoline, DPD/Cr; N-terminal cross-linked telopeptide of type 1 collagen, NTx/Cr; both corrected to urinary creatinine, Cr) were also measured.ResultsIn the trochanteric compared to the cervical group, females were older than males and the prevalence of Parkinson's disease, mean haemoglobin and albumin levels were lower. Incidence and degree of myocardial injury (cTnl rise) and inflammatory reaction (CRP elevation) as well as length of hospital stay, need of institutionalisation or in-hospital mortality were similar in both groups. Hypovitaminosis D (25(OH)D < 50 mmol/L) was present in 77.8% of patients with cervical and in 82.1% with trochanteric HF, elevated PTH (> 6.8 pmol/L) in 30.2% and 41.3%, respectively. The associations between 25(OH)D, PTH, and parameters of mineral metabolism and bone turnover were site-specific. In multivariate analyses, PTH (both as a continuous or categorical variable) response to hypovitaminosis D was a strong independent predictor of HF type. Coexistence of vitamin D deficiency (25(OH) D< 25 nmol/L) and elevated PTH predicts trochanteric HF while blunted PTH response predicts cervical HF (OR = 3.5; 95% CI 1.5–80; p = 0.005). PTH response and phosphate status (above or below median level) correctly discriminated HF type in 73.8% of patients with vitamin D deficiency.ConclusionsHF type is significantly associated with PTH response to hypovitaminosis D and impaired phosphate homeostasis. We detected only minor differences between two main HF types with regard to a wide range of clinical and routine laboratory variables as well as short-term outcomes.     

Optimizing tamoxifen-inducible Cre/loxp system to reduce tamoxifen effect on bone turnover in long bones of young mice

For tamoxifen-dependent Cre recombinase, also known as CreER recombinase, tamoxifen (TAM) is used to activate the Cre to generate time- and tissue-specific mouse mutants. TAM is a potent CreER system inducer; however, TAM is also an active selective estrogen receptor modulator (SERM) that can influence bone homeostasis. The purpose of this study was to optimize the TAM dose for Cre recombinase activation while minimizing the effects of TAM on bone turnover in young growing mice.MethodsTo evaluate the effects of TAM on bone turnover and bone mass, 1-month-old wild-type male and female mice were intraperitoneally injected with TAM at 0, 1, 10 or 100 mg/kg/day for four consecutive days, or 100, 300 mg/kg/day for one day. The distal femurs were analyzed one month after the last TAM injection by microCT, mechanical test, and surface-based bone histomorphometry. Similar doses of TAM were used in Col1 (2.3 kb)-CreERT2; mT/mG reporter male mice to evaluate the dose-dependent efficacy of Cre-ER activation in bone tissue.ResultsA TAM dose of 100 mg/kg × 4 days significantly increased trabecular bone volume/total volume (BV/TV) of the distal femur, femur length, bone strength, and serum bone turnover markers compared to the 0 mg control group. In contrast, TAM doses ≤ 10 mg/kg did not significantly change any of these parameters compared to the 0 mg group, although a higher bone strength was observed in the 10 mg group. Surface-based histomorphometry revealed that the 100 mg/kg dose of TAM dose significantly increased trabecular bone formation and decreased periosteal bone formation at 1-week post-TAM treatment. Using the reporter mouse model Col1-CreERT2; mT/mG, we found that 10 mg/kg TAM induced Col1-CreERT2 activity in bone at a comparable level to the 100 mg/kg dose.ConclusionsTAM treatment at 100 mg/kg/day × 4 days significantly affects bone homeostasis, resulting in an anabolic bone effect on trabecular bone in 1-month-old male mice. However, a lower dose of TAM at 10 mg/kg/day × 4 days can yield similar Col1-CreERT2 induction efficacy with minimum effects on bone turnover in young male mice.     

Reduced levels of serum IGF-1 is related to the presence of osteoporotic fractures in male idiopathic osteoporosis

IntroductionThe pathophysiology of male idiopathic osteoporosis (MIO) remains unknown. The aim of this study was to evaluate the involvement of IGF-1 in MIO, and to explore the relationships between bone mineral density and serum levels of IGF-1 and sex hormones.MethodsInclusion criteria were osteoporosis (T-score < ?2.5 SD) and/or an osteoporotic fracture. The osteoporotic patients were included after an exhaustive work-up to exclude the principal causes of secondary osteoporosis. Serum levels of IGF-1, estradiol, testosterone, SHBG, markers of bone turnover, and bone mineral density were compared between 79 MIO and 26 healthy subjects.ResultsA significant reduction in serum IGF-1 was found in MIO patients (p = 0.0189). This remained significant after adjustment for body mass index (BMI). A negative correlation was found between SHBG and serum IGF-1 (r = ?0.231, p = 0.048). SHBG levels were higher in osteoporotic patients (p = 0.001). The Free Testosterone Index (FTI, total testosterone/SHBG) (p = 0.002) was also lower in MIO patients. After adjustment for FTI and BMI, a significant association was observed between IGF-1 level and the presence of an osteoporotic fracture, indicating an independent effect of IGF-1 level on fracture risk. The odds ratio (OR) for fracture for each SD decrease in IGF1 level was 1.8 [CI: 1.09–2.96] (p = 0.021).ConclusionOur study indicates a decrease in serum IGF-1 levels in MIO. This could be either the cause or the consequence of a disturbance in sex hormone metabolism with increased SHBG serum levels.     

Effects of rhIGF-1 administration on surrogate markers of bone turnover in adolescents with anorexia nervosa

BackgroundAdolescents with anorexia nervosa (AN) have low bone density and low levels of surrogate markers of bone formation. Low bone density is a consequence of hormonal alterations that include hypogonadism and decreases in IGF-1, a bone trophic factor. Although IGF-1 is key to pubertal bone accretion, and effects have been demonstrated in adults, there are no data regarding the effect of recombinant human (rh) IGF-1 administration in adolescents with AN.ObjectivesWe hypothesized that rhIGF-1 would cause an increase in PINP, a bone formation marker, in girls with AN, without any effect on CTX, a bone resorption marker.Subjects and methodsRhIGF-1 was administered at a dose of 30–40 mcg/k twice daily to 10 consecutive girls with AN 12–18 years old for 7–9 days. Ten age-matched girls with AN were followed without rhIGF-1 for a similar period. IGF-1, PINP and CTX levels were measured.ResultsRhIGF-1 administration caused an increase in IGF-1 from day-1 to day-4/5 (p < 0.0001) and day-1 to day-8/9 (p < 0.0001). Simultaneously, PINP increased from day-1 to day-4/5 (p = 0.004) and day-1 to day-8/9 (p = 0.004), with a smaller increase from day-4/5 to day-8/9 (p = 0.048). CTX levels did not change with rhIGF-1 administration. No changes occurred in IGF-1 or PINP levels in girls not receiving rhIGF-1; however, CTX levels increased significantly (p = 0.01). Percent change in PINP was significantly higher (p = 0.02) and percent change in CTX was significantly lower (p = 0.006) in girls who received rhIGF-1 compared to those who did not receive any intervention. RhIGF-1 was well tolerated without hypoglycemia.ConclusionShort-term administration of rhIGF-1 causes an increase in a surrogate bone formation markers in girls with AN without significant side effects.     

Outcome of glucose homeostasis in patients with glucocorticoid-induced osteoporosis undergoing treatment with bone active-drugs

Over the last few years, there has been experimental evidence for the existence of cross-talking between bone remodeling and glucose metabolism. Whether this experimental model can be translated to humans is still debated, and it is also unclear whether the modulation of bone turnover by anti-osteoporotic drugs may lead to changes in glucose metabolism. The aim of this 12-month prospective study was to investigate whether treatment of glucocorticoid-induced osteoporosis (GIO) with bipshosphonates or teriparatide may influence serum glycated hemoglobin (HbA1c) and fasting plasma glucose. One-hundred-eleven patients (70 F, 41 M, median age 70, range: 55–89) chronically treated with glucocorticoids were evaluated for changes in serum HbA1c and fasting plasma glucose during treatment with bisphosphonates (45 cases) or teriparatide (33 cases) as compared to those occurring during treatment with calcium and vitamin D alone (33 cases).In patients treated with teriparatide, but not in those treated with bisphosphonates or calcium and vitamin D alone, a statistically significant (p =0.01) decrease in serum HbA1c was observed during the follow-up, the change being greater (p = 0.01) in patients with diabetes as compared to those without diabetes. In most cases, the decrease of serum HbA1c was relatively limited and in some patients the improvement of glucose homeostasis was concomitant with implementation of anti-diabetic treatments. Fasting plasma glucose did not change significantly during either bisphosphonates or teriparatide treatments.In conclusion, currently used bone active drugs may produce limited effects on glucose metabolism in patients with GIO. Interestingly, the bone anabolic drug teriparatide was shown to be associated with some improvement in serum HbA1c in this clinical context.     

Switching of oral bisphosphonates to denosumab in chronic glucocorticoid users: A 12-month randomized controlled trial

ObjectivesTo evaluate the effect of switching from oral bisphosphonates to denosumab on bone mineral density (BMD) in long-term glucocorticoid users.MethodsAdult patients who were receiving long-term prednisolone (≥ 2.5 mg/day for ≥ 1 year) and oral bisphosphonates (≥ 2 years) were recruited. Participants were randomized to either continue oral bisphosphonates or switch to denosumab (60 mg subcutaneously every 6 months) for 12 months. Serial BMD (lumbar spine, hip) and bone turnover markers (serum osteocalcin, P1NP, β-CTX) were measured.Results42 women were recruited (age 54.7 ± 12.9 years; 21 shifted to denosumab and 21 continued on bisphosphonates). The duration of prednisolone therapy was 101 ± 66.3 months and the daily dose was 4.4 ± 2.1 mg. Baseline demographic data, osteoporosis risk factors, and BMD at various sites were similar between the two groups of patients. At month 12, BMD of the spine and hip increased by + 3.4 ± 0.9% (p = 0.002) and + 1.4 ± 0.6% (p = 0.03), respectively, in the denosumab group; whereas the corresponding change was + 1.5 ± 0.4% (p = 0.001) and + 0.80 ± 0.5% (p = 0.12) in the bisphosphonate group. The spinal BMD at month 12 was significantly higher in the denosumab than bisphosphonate group after adjustment for baseline BMD and β-CTX values, and other confounding factors (p = 0.01). Bone turnover markers (β-CTX and P1NP) were more strongly suppressed by denosumab than the bisphosphonates. Minor infections were more common in denosumab-treated patients while other adverse events occurred at similar frequencies between the two groups.ConclusionsIn patients receiving long-term glucocorticoids, switching from oral bisphosphonates to denosumab resulted in greater gain of the spinal BMD and suppression of bone turnover markers after 12 months of therapy. The results have to be confirmed by a larger clinical trial with fracture as endpoint.     

Effect of propofol,sevoflurane, and isoflurane on postoperative cognitive dysfunction following laparoscopic cholecystectomy in elderly patients: A randomized controlled trial

Study objectiveTo compare the incidence of postoperative cognitive dysfunction (POCD) in elderly surgical patients (> 60 years) receiving different anesthetics (propofol, sevoflurane, or isoflurane) and to identify potential biomarkers of POCD in this patient population.DesignProspective, randomized, double-blind clinical trial.SettingUniversity-affiliated teaching hospital.PatientsOne hundred and fifty elderly patients scheduled for laparoscopic cholecystectomy.InterventionsElderly patients undergoing laparoscopic cholecystectomy were randomly assigned to receive propofol, sevoflurane, or isoflurane anesthesia. Measurements: Cognitive function was assessed using neuropsychological tests at baseline (1 day before surgery [D0]), and on postoperative day 1 (D1) and day 3 (D3). Plasma S-100β and Aβ_1–40 protein, IL-1β, IL-6 and TNF-α concentrations were assessed before induction of anesthesia (T0), after extubation (T1), and 1 h (T2) and 24 h (T3) postoperatively.Main resultsThe incidence of POCD was significantly lower in the propofol group compared to the isoflurane group and the sevoflurane group at D1 and D3 (propofol vs. isoflurane: D1 and D3, P < 0.001; propofol vs. sevoflurane: D1, P = 0.012; D3, P = 0.013). The incidence of POCD was significantly lower in the sevoflurane group compared to the isoflurane group at D1 ( P = 0.041), but not at D3. Postoperatively, plasma S-100β and Aβ_1–40 protein, IL-1β, IL-6, and TNF-α concentrations were significantly decreased in the propofol group compared to the isoflurane group.ConclusionsPropofol anesthesia may be an option for elderly surgical patients.     

Suggestive linkage to chromosome 1q for bone mineral apparent density in Brazilian sister adolescents

ObjectiveTo investigate linkage to chromosome 1q and 11q region for lumbar spine, femoral neck and total body BMD and volumetric BMD in Brazilian sister adolescents aged 10–20-year-old and 57 mothers.MethodsWe evaluated 161 sister pairs (n = 329) aged 10–20 years old and 57 of their mothers in this study. Physical traits and lifestyle factors were collected as covariates for lumbar spine (LS), femoral neck (FN) and total body (TB) BMD and bone mineral apparent density (BMAD). We selected nine microsatellite markers in chromosome 1q region (spanning nearly 33cM) and eight in chromosome 11q region (spanning nearly 34cM) to perform linkage analysis.ResultsThe highest LOD score values obtained from our data were in sister pairs LS BMAD analysis. Their values were: 1.32 (P < 0.006), 2.61 (P < 0.0002) and 2.44 (P < 0.0004) in D1S218, D1S2640 and D1S2623 markers, respectively. No significant LOD score was found with LS and FN BMD/BMAD in chromosome 11q region. Only TB BMD showed significant linkage higher than 1.0 for chromosome 11q region in the markers D11S4191 and D11S937.Discussion/ConclusionsOur results provided suggestive linkage for LS BMAD at D1S2640 marker in adolescent sister pairs and suggest a possible candidate gene (LHX4) related to adolescent LS BMAD in this region. These results reinforce chromosome 1q21-23 as a candidate region to harbor one or more bone formation/maintenance gene. In the other hand, it did not repeat for chromosome 11q12-13 in our population.     

Effects of soy isoflavone supplements on bone turnover markers in menopausal women: Systematic review and meta-analysis of randomized controlled trials

IntroductionEffects of soy isoflavone supplements on bone turnover markers remain unclear. This up-to-date systematic review and meta-analysis of randomized controlled trials (RCTs) was performed primarily to more completely and precisely clarify the effects on urinary deoxypyridinoline (DPD) and serum bone alkaline phosphatase (BAP) and secondarily to evaluate the effects on other bone turnover markers, compared with placebo in menopausal women.MethodsPubMed, CENTRAL, ICHUSHI, and CNKI were searched in June 2009 for relevant studies of RCTs. Data on study design, participants, interventions, and outcomes were extracted and methodological quality of each included trial was assessed.ResultsFrom 3740 identified relevant articles, 10 (887 participants), 10 (1210 participants), and 8 (380 participants) RCTs were selected for meta-analysis of effects on DPD, BAP, and serum osteocalcin (OC), respectively, using Review Manager 5.0.22. Daily ingestion of an average 56 mg soy isoflavones (aglycone equivalents) for 10 weeks to 12 months significantly decreased DPD by 14.1% (95% CI: ? 26.8% to ? 1.5%; P = 0.03) compared to baseline (heterogeneity: P < 0.00001; I² = 93%; random effects model). The overall effect of soy isoflavones on DPD compared with placebo was a significant decrease of ? 18.0% (95% CI: ? 28.4% to ? 7.7%, P = 0.0007; heterogeneity: P = 0.0001; I² = 73%; random effects model). Subgroup analyses and meta-regressions revealed that isoflavone dose and intervention duration did not significantly relate to the variable effects on DPD. Daily supplementation of about 84 mg and 73 mg of soy isoflavones for up to 12 months insignificantly increased BAP by 8.0% (95% CI: ? 4.2% to 20.2%, P = 0.20; heterogeneity: P < 0.00001; I² = 98%) and OC by 10.3% (95% CI: ? 3.1% to 23.7%, P = 0.13; heterogeneity: P = 0.002; I² = 69%) compared with placebo (random effects model), respectively.ConclusionsSoy isoflavone supplements moderately decreased the bone resorption marker DPD, but did not affect bone formation markers BAP and OC in menopausal women. The effects varied between studies, and further studies are needed to address factors relating to the observed effects of soy isoflavones on DPD and to verify effects on other bone turnover markers.     

Lidocaine-tramadol versus lidocaine-dexmedetomidine for intravenous regional anesthesia

BackgroundIntravenous regional anesthesia (IVRA) has been used for more than a century. Both tramadol (synthetic opioid) and dexmedetomidine (α₂-agonist) can act locally.Aim of the workTo compare effects of adding tramadol versus dexmedetomidine to lidocaine during IVRA.Patients and methodsSixty patients were randomly assigned into: Group C (n = 20), Group T (n = 20), and Group D (n = 20). All patients received 3 mg/kg 0.5% lidocaine [+100 mg tramadol in Group T, or 1 μg/kg dexmedetomidine in Group D]. Times of onset and offset of sensory and motor blocks, and time to tourniquet pain were recorded. Postoperative VAS score, time to first dose, and total amounts of supplementary analgesia (Paracetamol) were recorded. Sedation was evaluated using Ramsay sedation scale (RSS).ResultsSignificantly shorter onset times and longer recovery times of sensory and motor block were recorded in Groups T and D compared to Group C (P < 0.05); while, with no significant differences between Groups T and D. Delayed onset of tourniquet pain occurred in Groups T and D compared to Group C (P < 0.05) with no significant differences between Groups T and D. Fourteen patients required fentanyl to control tourniquet pain in Group C compared to (5 and 4) in Groups T and D respectively. Significantly lower Postoperative VAS score, longer time to first dose and lower consumption of Paracetamol were recorded in Groups T and D than in Group C; with no significant differences between Groups T and D. Complications were skin rash in 30% of patients in Group T, bradycardia and sedation in 35% and 65% of patients in Group D respectively.ConclusionAddition of either tramadol or dexmedetomidine enhances lidocaine during IVRA with higher incidence of skin rash with tramadol and postoperative bradycardia and sedation with dexmedetomidine.