Bone metabolism in galactosemia

Classical galactosemia is an autosomal recessively inherited disorder of galactose metabolism. Treatment consists of life-long dietary restriction of galactose. Despite treatment, long-term complications occur such as a decreased bone mineral density (BMD). A decreased BMD might be the result of either dietary deficiencies secondary to the galactose-restricted diet or unknown intrinsic factors. In this study, 40 children with classical galactosemia (13 males and 27 females, aged 3-17 years) on dietary treatment were included to gain insight in the bone metabolism of galactosemics. We found weight and height Z scores significantly decreased in galactosemics. Mean areal BMD Z scores of lumbar spine and of femoral neck as measured by Dual energy X-ray Absorptiometry (DXA) were -0.6 (P < 0.001) and -0.3 (P = 0.066), respectively. Mean volumetric BMD of the femoral neck was significant lower in galactosemics (P < 0.001). The recommended dietary allowances (RDA) for calcium, magnesium, zinc, vitamin D, and protein were met in all patients. Mean serum levels of calcium, phosphate, magnesium, zinc, 1,25-dihydroxy vitamin D (1,25OHD), parathormone (PTH), 17-beta estradiol, bone alkaline phosphatase (BAP), and under-carboxylated osteocalcin (ucOC) were normal. Serum levels of IGF-1 Z score, carboxylated osteocalcin (cOC), N-terminal telopeptide (NTX), and C-terminal telopeptide (CTX) were significantly lower in galactosemics than in control subjects. The different bone markers were strongly correlated. The low levels of IGF-1 Z score, formation marker cOC, and resorption markers NTX and CTX suggest a decreased bone metabolism in galactosemics.     

Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women

Summary

We have investigated whether low-dose vitamin K2 supplements (menaquinone-7, MK-7) could beneficially affect bone health. Next to an improved vitamin K status, MK-7 supplementation significantly decreased the age-related decline in bone mineral density and bone strength. Low-dose MK-7 supplements may therefore help postmenopausal women prevent bone loss.

Introduction

Despite contradictory data on vitamin K supplementation and bone health, the European Food Safety Authorities (EFSA) accepted the health claim on vitamin K’s role in maintenance of normal bone. In line with EFSA’s opinion, we showed that 3-year high-dose vitamin K1 (phylloquinone) and K2 (short-chain menaquinone-4) supplementation improved bone health after menopause. Because of the longer half-life and greater potency of the long-chain MK-7, we have extended these investigations by measuring the effect of low-dose MK-7 supplementation on bone health.

Methods

Healthy postmenopausal women (n?=?244) received for 3 years placebo or MK-7 (180 μg MK-7/day) capsules. Bone mineral density of lumbar spine, total hip, and femoral neck was measured by DXA; bone strength indices of the femoral neck were calculated. Vertebral fracture assessment was performed by DXA and used as measure for vertebral fractures. Circulating uncarboxylated osteocalcin (ucOC) and carboxylated OC (cOC) were measured; the ucOC/cOC ratio served as marker of vitamin K status. Measurements occurred at baseline and after 1, 2, and 3 years of treatment.

Results

MK-7 intake significantly improved vitamin K status and decreased the age-related decline in BMC and BMD at the lumbar spine and femoral neck, but not at the total hip. Bone strength was also favorably affected by MK-7. MK-7 significantly decreased the loss in vertebral height of the lower thoracic region at the mid-site of the vertebrae.

Conclusions

MK-7 supplements may help postmenopausal women to prevent bone loss. Whether these results can be extrapolated to other populations, e.g., children and men, needs further investigation.     

Pamidronate preserves bone mass for at least 2 years following acute administration for pediatric burn injury

We have previously shown that pamidronate, when given within 10 days of burn injury, preserves lumbar spine bone mineral content from admission to discharge in 6-8 weeks and at 6 months increases both lumbar spine and total body bone mineral content (BMC) over placebo. We followed patients unblinded after 6 months every 3 months up to 2 years post-burn to see if the effects of pamidronate were sustained. Additionally, we assessed bone remodeling at 1 year post-burn by iliac crest bone biopsy. We enrolled 57 subjects who were initially randomized to pamidronate (n=32) and placebo (n=25). After 2 years, 21 subjects (pamidronate=8, placebo=13) remained. Analysis of bone densitometry by dual energy X-ray absorptiometry revealed an effect of both treatment (p<0.012 for total body BMC, p<0.001 for lumbar spine BMC, p<0.014 for lumbar spine bone area and p<0.003 for lumbar spine bone density (BMD)) and time (p<0.0003 on total body BMC, p<0.001 on lumbar spine BMC, p<0.001 on lumbar spine bone area, and no significant difference on lumbar spine BMD). There was no interaction between treatment and time. Results for bone histomorphometry revealed no effect of treatment on either static or dynamic parameters but did show an effect of time on osteoid area (p=0.004, surface p<0.001, and width, p<0.001). We conclude that acute administration of pamidronate resulted in sustained therapeutic effect on bone and that this type of administration may serve as a useful adjunct to other therapies in the preservation and augmentation of bone mass following severe burns.     

维生素K2防治绝经后骨质疏松症作用的荟萃分析

目的 为了确定维生素K2对绝经后骨质疏松症(postmenopausal osteoporosis, PMOP)患者的预防和治疗作用,我们对22项随机对照试验进行了荟萃分析。方法 在PubMed、Cochrane Library、Embase数据库和三个中文数据库(CBM、CNKI和万方)检索了2020年6月1日之前发布的相关随机对照试验(RCT),以维生素K2与安慰剂或其他抗骨质疏松药物预防和治疗PMOP进行比较。使用固定效应或随机效应模型计算合并风险比(RR)、平均值(MD)和95％置信区间(CI)。结果 包括7 154名绝经女性参与的22项随机对照试验符合纳入标准。补充维生素K2 12个月后改善绝经后女性腰椎骨密度优于对照组(P = 0.03),PMOP亚组腰椎骨密度改善较对照组差异有统计学意义 (P = 0.03)。补充维生素K2预防绝经后女性椎体骨折发生率优于对照组(RR = 0.52, 95 % CI: 0.36~0.74, P = 0.003),PMOP亚组椎体骨折发生率低于对照组(P = 0.006)。补充维生素K2显著降低低羧化骨钙素(ucOC)(P <0.001)。补充维生素K2药物不良反应略高于对照组(RR=1.29, 95 % CI:1.03~1.63, P = 0.03)。结论 补充维生素K2 12个月后有效改善绝经后女性腰椎骨密度,预防椎体骨折,降低ucOC,PMOP患者获益更大。口服维生素K2被认为是安全的。     

Enhanced bone mass and physical fitness in prepubescent footballers

Not much is known about the osteogenic effects of sport activities before puberty. We tested the hypothesis that football (soccer) participation is associated with enhanced bone mineral content (BMC) and areal density (BMD) in prepubertal boys. One hundred four healthy white boys (9.3 +/- 0.2 years, Tanner stages I-II) participated in this study: 53 footballers and 51 controls. The footballers devoted at least 3 h per week to participation in football, while the controls did not perform in any kind of regular physical activity other than that programmed during the compulsory physical education courses. Bone variables were measured by dual-energy X-ray absorptiometry. The maximal leg extension isometric force in the squat position with knees bent at 90 degrees and the peak force, mean power, and height jumped during vertical jumps were assed with a force plate. Additionally, 30-m running speed, 300-m run (anaerobic capacity), and 20-m shuttle-run tests (maximal aerobic power) were also performed. Compared to the controls, the footballers attained better results in the physical fitness test and had lower body mass (-10%, P < 0.05) due to a reduced percentage of body fat (4% less, P < 0.05). The footballers exhibit enhanced trochanteric BMC (+17%, P < 0.001). Likewise, femoral and lumbar spine BMD were also greater in the football players (P 相似文献   

Bone mineral density in prepubertal obese and control children: relation to body weight,lean mass,and fat mass

The aim of the study was to determine the influence of obesity on bone status in prepubertal children. This study included 20 obese prepubertal children (10.7 +/- 1.2 years old) and 23 maturation-matched controls (10.9 +/- 1.1 years old). Bone mineral area, bone mineral content (BMC), bone mineral density (BMD), and calculation of bone mineral apparent density (BMAD) at the whole body and lumbar spine (L1-L4) and body composition (lean mass and fat mass) were assessed by DXA. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) at the calcaneus were measured with a BUA imaging device. Expressed as crude values, DXA measurements of BMD at all bone sites and BUA (69.30 versus 59.63 dB/MHz, P < 0.01) were higher in obese children. After adjustment for body weight and lean mass, obese children displayed lower values of whole-body BMD (0.88 versus 0.96 g/cm2, P < 0.05) and BMC (1190.98 versus 1510.24 g, P < 0.01) in comparison to controls. When results were adjusted for fat mass, there was no statistical difference between obese and control children for DXA and ultrasound results. Moreover, whole-body BMAD was lower (0.086 versus 0.099 g/cm3, P < 0.0001), whereas lumbar spine BMAD was greater (0.117 versus 0.100 g/cm3, P < 0.001) in obese children. Thus, it was observed that, in obese children, cortical and trabecular bone displayed different adaptation patterns to their higher body weight. Cortical bone seems to enhance both size and BMC and trabecular bone to enhance BMC. Finally, considering total body weight and lean mass of obese children, these skeletal responses were not sufficient to compensate for the excess load on the whole body.     

Risedronate Increases Bone Density and Reduces Vertebral Fracture Risk Within One Year in Men on Corticosteroid Therapy

Limited information is available on the effect of bisphosphonates in men receiving corticosteroid therapy. We studied 184 men among the patients enrolled in two, double-blind, placebo-controlled, 1-year studies with similar protocols. The studies evaluated the effects of risedronate in patients beginning corticosteroid treatment at a dose of at least 7.5 mg per day of prednisone or equivalent (prevention study) or continuing long-term treatment of corticosteroid at that dose (treatment study). The men received either placebo or risedronate (2.5 mg or 5 mg) daily, along with calcium supplementation (500-1000 mg). Endpoints included differences in bone mineral density (BMD) at the lumbar spine, femoral neck, and femoral trochanter, assessment of vertebral fractures, changes in biochemical markers of bone turnover, and overall safety. In the treatment study, risedronate 5 mg significantly (P < 0.01) increased lumbar spine BMD by 4.8% at the lumbar spine, 2.1% at the femoral neck, and 2.6% at the femoral trochanter compared with baseline values. In the prevention study, bone loss was prevented with risedronate 5 mg; in the placebo group, BMD decreased significantly (P < 0.01) by 3.4%, 3.3%, and 3.4% in the lumbar spine, femoral neck, and trochanter, respectively, at 1 year. The differences between risedronate 5 mg and placebo groups were significant at all skeletal sites in the prevention study (P < 0.01) and at the lumbar spine in the treatment study (P < 0.001). The 2.5 mg dose also had a positive effect on BMD, although of a lesser magnitude than the 5 mg dose. When the data from the two studies were combined, the incidence of vertebral fractures decreased 82.4% (95% confidence interval, 36.6%-95.1%) in the pooled risedronate groups compared with placebo (P = 0.008). Risedronate was well tolerated in men, with a similar incidence of upper gastrointestinal adverse events in the placebo and treatment groups. Daily treatment with risedronate increases bone density and decreases vertebral fracture risk within 1 year in men receiving corticosteroid therapy.     

Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women.

Dietary supplementation with vitamin K(1), with vitamin D(3) and calcium or their combination, was examined in healthy older women during a 2-year, double-blind, placebo-controlled trial. Combined vitamin K with vitamin D plus calcium was associated with a modest but significant increase in BMC at the ultradistal radius but not at other sites in the hip or radius. INTRODUCTION: The putative beneficial role of high dietary vitamin K(1) (phylloquinone) on BMD and the possibility of interactive benefits with vitamin D were studied in a 2-year double-blind, placebo-controlled trial in healthy Scottish women > or =60 years of age. MATERIALS AND METHODS: Healthy, nonosteoporotic women (n = 244) were randomized to receive either (1) placebo, (2) 200 microg/day vitamin K(1), (3) 10 microg (400 IU) vitamin D(3) plus 1000 mg calcium/day, or (4) combined vitamins K(1) and D(3) plus calcium. Baseline and 6-month measurements included DXA bone mineral scans of the hip and wrist, markers of bone turnover, and vitamin status. Supplementation effects were tested using multivariate general linear modeling, with full adjustment for baseline and potential confounding variables. RESULTS: Significant bone mineral loss was seen only at the mid-distal radius but with no significant difference between groups. However, women who took combined vitamin K and vitamin D plus calcium showed a significant and sustained increase in both BMD and BMC at the site of the ultradistal radius. Serum status indicators responded significantly to respective supplementation with vitamins K and D. Over 2 years, serum vitamin K(1) increased by 157% (p < 0.001), the percentage of undercarboxylated osteocalcin (%GluOC) decreased by 51% (p < 0.001), serum 25-hydroxyvitamin D [25(OH)D] increased by 17% (p < 0.001), and PTH decreased by 11% (p = 0.049). CONCLUSIONS: These results provide evidence of a modest synergy in healthy older women from nutritionally relevant intakes of vitamin K(1) together with supplements of calcium plus moderate vitamin D(3) to enhance BMC at the ultradistal radius, a site consisting of principally trabecular bone. The substantial increase in gamma-carboxylation of osteocalcin by vitamin K may have long-term benefits and is potentially achievable by increased dietary intakes of vitamin K rather than by supplementation.     

The effect of fluoride and calcium on spinal bone mineral content: A controlled,prospective (3 years) study

Summary Daily treatment with 30 mg of sodium fluoride (NaF) and 1 g of calcium over a 3-year period increased the bone mineral content (BMC) in the spines of women (n=25) with osteoporosis. Determination of the BMC was followed with dual photon absorptiometry (¹³⁷Cs-²⁴¹Am) in the third lumbar vertebra. No increase in BMC was found with only 10 mg sodium fluoride in combination with calcium (n=25), with calcium alone (n=25), or with placebo (n=25). No serious side effects were registered. There was, however, minor gastrointestinal distress in one-fifth of the patients taking 30 mg NaF daily.     

Bone response to jumping is site-specific in children: a randomized trial

Skeletal loading during growth may be one way of increasing bone mass early in life. We hypothesized that children randomized to a jumping program (25 jumps/day from a 45-cm box, 5 days/week for 12 weeks) would have greater increases in hip and spine bone mineral content (BMC) and 4% distal tibia volumetric bone density than children randomized to the control group. Our secondary hypothesis was that jumping would not be as beneficial among peripubertal children as compared to prepubertal or pubertal children due to the relatively high growth rate that occurs during the peripubertal period. Fifty-four children (31 girls) ages 3-5, 7-8, 11-12, and 15-18 years were enrolled. We performed bone, anthropometric, and force plate measurements at baseline and 12 weeks. Twenty-four-hour diet recall and Tanner's self-report of pubertal development were completed at baseline. Jumpers had a lower calcium intake than nonjumpers at baseline (965 +/- 403 vs 1295 +/- 465 mg/day, P < 0.01), but the groups were otherwise similar. Overall, jumpers had greater increases in total body BMC (45.0 +/- 4.9 vs 29.4 +/- 5.3 g, P = 0.03) and regional dual energy x-ray absorptiometry leg BMC (19.8 +/- 2.6 vs 11.5 +/- 2.8 g, P = 0.03) than nonjumpers at all pubertal stages. However, the 4% distal tibia bone response to jumping appeared to be modified by pubertal stage, with the greatest bone benefit from jumping observed in pubertal children (interaction of jumping group by pubertal stage, P < 0.05, for both BMC and volumetric BMD). A similar pattern was observed for spine BMC (interaction, P = 0.10). We conclude that skeletal loading increases total body and leg BMC in children, but may not have a positive effect at sites that are predominantly trabecular bone during periods of rapid growth (i.e., peripubertal period).     

Effects of Intranasal Salmon Calcitonin in Juvenile Idiopathic Arthritis: An Observational Study

The aim of this study was to follow the changes in bone mineral density (BMD) and biochemical markers of bone turnover in 10 children (7.5-17.5 years of age) with severe juvenile idiopathic arthritis (JIA), during a 3-year therapy with salmon calcitonin (100 IU/day 2 months on and 2 off for a year and 200 IU/day for 2 years) and calcium (500 mg/day). All patients were functional classes III and IV and were measured at yearly intervals with a dual photon absorptiometer at the lumbar spine. The changes observed were 7.2-9.5% per year for BMD and 2.0-6.0% for volumetric bone mineral density (BMDvol). The bone resorption markers showed significant decreases after a year's treatment (Pyr/Cr from 175+/-15 to 108+/-15 nm/mm, P < 0.001, Pyr-D/Cr from 24.3+/-3.5 to 13.3+/-1.9 nm/mm, P < 0.05, and OHPr/Cr from 57.4+/-11 to 35.1+/-8.4 microg/mg) and smaller changes thereafter. No significant changes were observed in the bone formation markers of osteocalcin and alkaline phosphatase. Serum iPTH, the vitamin D metabolites, and calcium concentrations fluctuated within normal, while calcium excretion increased from 0.3+/-0.1 to 1.9+/-0.4 mg/kg/24 hours, P < 0.001. In conclusion, the present study, despite its limitations of not being placebo controlled, shows possible beneficial effects of intranasal calcitonin on bone resorption and pain relief in JIA patients.     

Epimedium-derived phytoestrogen flavonoids exert beneficial effect on preventing bone loss in late postmenopausal women: a 24-month randomized, double-blind and placebo-controlled trial.

Epimedium brevicornum maxim, a nonleguminous medicinal plant, has been found to be rich in phytoestrogen flavonoids. Results from a 24-month randomized double-blind placebo-controlled clinical trial showed that Epimedium-derived phytoestrogen flavonoids were able to exert beneficial effects on preventing bone loss in late postmenopausal women, without resulting in a detectable hyperplasia effect on the endometrium. INTRODUCTION: We performed a 24-mo randomized double-blind placebo-controlled clinical trial for evaluating the effect of the Epimedium-derived phytoestrogen flavonoids (EPFs) on BMD, bone turnover biochemical markers, serum estradiol, and endometrial thickness in postmenopausal women. MATERIALS AND METHODS: One hundred healthy late postmenopausal women, with a natural menopausal history within 10 approximately 18 yr and with a BMD T-score at the lumbar spine between -2 and -2.5 SD, were randomized into EPF treatment group (n = 50; a daily dose of 60 mg Icariin, 15 mg Daidzein, and 3 mg Genistein) or placebo control group (n = 50). All participants received 300 mg element calcium daily. BMD, bone turnover biochemical markers, serum estradiol, and endometrial thickness were measured at baseline and 12 and 24 mo after intervention. RESULTS: Eighty-five participants completed the trial. The patterns of BMD changes were significantly different between the EPF treatment group and placebo control group by repeated-measures ANOVA (p = 0.045 for interaction between time and group at femoral neck; p = 0.006 for interaction between time and group at lumbar spine). BMD was found with a decreased tendency in the placebo control group at 12 (femoral neck: -1.4%, p = 0.104; lumbar spine: -1.7%, p = 0.019) and 24 mo (femoral neck: -1.8%, p = 0.048; lumbar spine: -2.4%, p = 0.002), whereas EPF treatment maintained BMD at 12 (femoral neck: 1.1%, p = 0.285; lumbar spine:1.0%, p = 0.158) and 24 mo (femoral neck: 1.6%, p = 0.148; lumbar spine: 1.3%, p = 0.091). The difference in lumbar spine between the two groups was significant at both 12 (p = 0.044) and 24 mo (p = 0.006), whereas the difference in the femoral neck was marginal at 12 mo (p = 0.061) and significant at 24 mo (p = 0.008). Levels of bone biochemical markers did not change in the placebo control group. In contrast, EPF intervention significantly decreased levels of deoxypyrdinoline at 12 (-43%, p = 0.000) and 24 mo (-39%, p = 0.000), except for osteocalcin at 12 (5.6%, p = 0.530) and 24 mo (10.7%, p = 0.267). A significant difference in deoxypyrdinoline between the two groups was found at both 12 (p = 0.000) and 24 mo (p = 0.001). Furthermore, neither serum estradiol nor endometrial thickness was found to be changed in either groups during the clinical trial. CONCLUSIONS: EPFs exert a beneficial effect on preventing bone loss in late postmenopausal women without resulting in a detectable hyperplasia effect on the endometrium.     

Carboxylated and intact osteocalcin predict adiponectin concentration in hemodialyzed patients

Purpose Disrupted bone metabolism in patients with chronic kidney disease (CKD) is associated with elevated concentrations of biochemical bone markers. Recently, animal studies show the role of osteocalcin in energy metabolism, which is partially confirmed in humans. The aim of our study was to evaluate the relationships between serum concentrations of bone markers and indices of energy metabolism in CKD patients on maintenance hemodialysis; in particular, the relationship between various forms of osteocalcin and adiponectin. Patients and methods The cross-sectional study included 155 hemodialyzed stage 5 CKD patients. Serum concentrations of glucose, insulin, adiponectin, bone alkaline phosphatase (bALP), tartrate resistant acid phosphatase (TRAP), carboxylated (cOC), undercarboxylated (ucOC), and intact osteocalcin (OC) were determined. Results In total cohort, bALP, TRAP, cOC, and ucOC negatively correlated with BMI. All analyzed bone markers positively correlated with adiponectin in total cohort and in men. In multiple linear regression analysis including all patients, log(cOC) and log(intact OC) were the only bone markers that predicted log(adiponectin) (beta?=?0.22; p?=?0.016 and beta?=?0.26; p?=?0.010) independently of sex, dialysis vintage, CRP, insulin, iPTH concentrations, BMI, and age. Conclusions Our data confirm the positive association between cOC, intact OC, and adiponectin concentrations in CKD patients on maintenance hemodialysis.     

A positive dose-response effect of vitamin D supplementation on site-specific bone mineral augmentation in adolescent girls: a double-blinded randomized placebo-controlled 1-year intervention.

The effect of vitamin D supplementation on bone mineral augmentation in 212 adolescent girls with adequate calcium intake was studied in a randomized placebo-controlled setting. Bone mineral augmentation determined by DXA increased with supplementation both in the femur and the lumbar vertebrae in a dose-responsive manner. Supplementation decreased the urinary excretion of resorption markers, but had no impact on formation markers. INTRODUCTION: Adequate vitamin D intake protects the elderly against osteoporosis, but there exists no indisputable evidence that vitamin D supplementation would benefit bone mineral augmentation. The aim of this 1-year study was to determine in a randomized double-blinded trial the effect of 5 and 10 microg vitamin D3 supplementation on bone mineral augmentation in adolescent girls with adequate dietary calcium intake. MATERIALS AND METHODS: Altogether, 228 girls (mean age, 11.4 +/- 0.4 years) participated. Their BMC was measured by DXA from the femur and lumbar spine. Serum 25-hydroxyvitamin D [S-25(OH)D], intact PTH (S-iPTH), osteocalcin (S-OC), and urinary pyridinoline (U-Pyr) and deoxypyridinoline (U-Dpyr) were measured. Statistical analysis was performed both with the intention-to-treat (IT) and compliance-based (CB) method. RESULTS: In the CB analysis, vitamin D supplementation increased femoral BMC augmentation by 14.3% with 5 microg and by 17.2% with 10 microg compared with the placebo group (ANCOVA, p = 0.012). A dose-response effect was observed in the vertebrae (ANCOVA, p = 0.039), although only with the highest dose. The mean concentration of S-25(OH)D increased (p < 0.001) in the 5-microg group by 5.7 +/- 15.7 nM and in the 10-microg group by 12.4 +/- 13.7 nM, whereas it decreased by 6.7 +/- 11.3 nM in the placebo group. Supplementation had no effect on S-iPTH or S-OC, but it decreased U-DPyr (p = 0.042). CONCLUSIONS: Bone mineral augmentation in the femur was 14.3% and 17.2% higher in the groups receiving 5 and 10 microg of vitamin D, respectively, compared with the placebo group, but only 10 mug increased lumbar spine BMC augmentation significantly. Vitamin D supplementation decreased the concentration of bone resorption markers, but had no impact on bone formation markers, thus explaining increased bone mineral augmentation. However, the positive effects were noted with the CB method but not with IT.     

Nandrolone decanoate and intranasal calcitonin as therapy in established osteoporosis

This study used a randomized, 2 × 2 factorial design to evaluate over 2 years the effect of intranasal salmon calcitonin and intramuscular nandrolone decanoate on bone mass in elderly women with established osteoporosis. The study was double masked in relation to calcitonin and open in relation to nandrolone decanoate. One hundred and twenty-three women aged 60–88 years who had sustained a previous osteoporotic fracture, or had osteopenia, were recruited through an outpatient clinic. Women were assigned to one of four groups: (1) daily placebo nasal spray, (2) 400 IU intranasal calcitonin daily, (3) 20 intramuscular injections of 50 mg nandrolone decanoate (given as two courses of 10 injections) plus placebo nasal spray, or (4) 20 injections of 50 mg nandrolone decanoate plus 400 IU intranasal calcitonin daily. All subjects received 1000 mg calcium supplementation daily. Outcomes measured included changes in bone mineral density (BMD) at the lumbar spine, as measured by dual-energy quantitative computed tomography (DEQCT), in BMD of the proximal femur, and BMD and bone mineral content (BMC) of the lumbar spine and forearm, as measured by dual-energy X-ray absorptiometry (DXA). Significant positive changes from baseline in DXA BMC at the lumbar spine were observed over 2 years in the calcitonin group (5.0±1.9%, mean ± SE) and in the nandrolone deconate group (4.7±1.9%) but not in the placebo group (1.1±2.2%) or the combined therapy group (0.7±1.8%). Modelling based on the 2×2 factorial design revealed that nandrolone decanoate was associated with a 3.8±1.8% (p<0.05) gain in DXA BMD at the proximal femur. Modelling also revealed that calcitonin treatment was associated with a loss of 11.5±4.7% in DEQCT BMD at the lumbar spine and a loss of 3.7±1.8% in DXA BMD at the proximal femur (p<0.05). There was in vivo antagonism between the two medications of 7.9±3.9% for DXA BMC at the lumbar spine. Both agents caused positive changes from baseline in lumbar spine BMC. Nandrolone decanoate had beneficial effects on BMD at the proximal femur. This dose of intranasal calcitonin was associated with deleterious effects on trabecular BMD at the lumbar spine and total BMD at the proximal femur. There may be significant clinical antagonism between these two medications.     

Effect of growth hormone therapy and puberty on bone and body composition in children with idiopathic short stature and growth hormone deficiency

The state of bone health and the effect of growth hormone (GH) therapy on bone and body composition in children with idiopathic short stature (ISS) are largely unknown. A direct role of GH deficiency (GHD) on bone density is controversial. Using dual-energy X-ray absorptiometry, this study measured total body bone mineral content (TB BMC), body composition, and volumetric bone mineral density (vBMD) at the lumbar spine (LS) and femoral neck (FN) in 77 children (aged 3-17 years) with ISS (n = 57) and GHD (n = 20). Fifty-five children (GHD = 13) receiving GH were followed over 24 months including measurement of bone turnover. At diagnosis, size-corrected TB BMC SDS was greater (P 相似文献   

Calcium and vitamin D for osteoprotection in children with new-onset nephrotic syndrome treated with steroids: a prospective,randomized, controlled,interventional study

Background

There are no robust guidelines on strategies to prevent the adverse skeletal effects of glucocorticoids in children.

Objectives

To evaluate the role of prophylactic calcium and vitamin D on bone health in children with new-onset nephrotic syndrome (NS) treated with short-term (12 weeks), high-dose glucocorticoids.

Methods

Prospective, randomized, controlled, single blind, interventional study conducted on 41 steroid-naïve pre-pubertal children (29 boys, 12 girls). All children received prednisolone for 12 weeks (60 mg/m²/day daily for 6 weeks, followed by 40 mg/m²/day alternate days for 6 weeks). Recruited children were randomized into the intervention group (IG; vitamin D 1,000 IU/day and elemental calcium 500 mg/day) and the control group (CG). Bone mineral content (BMC) and bone mineral density (BMD) at the lumbar spine (L1–L4) were estimated at baseline and at 12 weeks. Mean percentage changes in BMC and BMD in IG and CG were compared.

Results

Children in the IG showed an increase of 11.2 % in BMC versus the CG, who showed an 8.9 % fall (p?<?0.0001). Net intervention-attributable difference in BMC was 20.1 %. BMD increased in both groups (IG 2.8 % vs CG 0.74 %), but the difference was not statistically significant (p?=?0.27).

Conclusions

Short-term, high-dose glucocorticoid therapy decreases the BMC of the lumbar spine in steroid-naïve children with NS. Vitamin D and calcium co-administration not only prevents this decline, but also enhances BMC of the lumbar spine.     

A systematic review of the effect of alendronate on bone mineral density in men.

Alendronate is known to increase bone mineral density (BMD) at the lumbar spine and hip in women, but less information is available in men. We conducted a systematic review of randomized controlled trials to determine whether oral alendronate improves BMD at the lumbar spine and hip in men with low bone mass or prevalent fractures, compared with men treated with placebo, calcium, or vitamin D. In three trials in men, BMD (measured by dual-energy X-ray absorptiometry) increased at 2-3 yr (compared to baseline) at the lumbar spine and femoral neck in alendronate-treated patients compared to controls. The pooled estimates of changes in BMD with 10 mg of alendronate daily compared to controls were as follows: 7.8% over 2-3 yr (95% confidence interval [CI] = 4.8- 10.8) at the lumbar spine and 3.8% (95% CI = 2.3-5.3) at the femoral neck (p < 0.001 for treatment effect in each analysis). Statistically significant heterogeneity of treatment effect was noted between trials. We conclude that 10 mg of oral daily alendronate is significantly associated with increase in BMD at the lumbar spine and hip in men over 2-3 yr and that these changes are similar to those previously observed in postmenopausal women.     

Effects of 24 Months of Growth Hormone (GH) Treatment on Serum Carboxylated and Undercarboxylated Osteocalcin Levels in GH-Deficient Adults

We studied the effect of growth hormone (GH) replacement on bone mineral density (BMD) and some parameters of bone metabolism, including undercarboxylated osteocalcin (ucOC), an independent predictive marker of fracture risk, which has not been previously determined or compared during GH treatment. Measurements were performed at baseline and after 6, 12, 18 and 24 months of the initiation of the GH therapy in 21 adult patients with GH deficiency. Significant increases were observed in BMD after 1 year at the lumbar spine and after 1.5 years at the femoral neck. Serum total OC and carboxylated (c) OC increased and reached the maximum at 6 months, but the values remained over the baseline at both 12 and 18 months. The ucOC:total OC ratio changed contrarily: it decreased at 6 months, then increased again and reached the baseline level during the next 18 months. Serum calcium (Ca), phosphate (P) and total alkaline phosphatase (ALP) levels increased after 6 months, thereafter the Ca and P values decreased, while the total ALP remained elevated until 12 months. Serum parathormone decreased at 12 months and increased again thereafter. GH replacement therapy is associated with improvement of ucOC, a marker of fracture risk, which in addition to the increase of BMD, might contribute to the beneficial effect of GH replacement therapy on bone metabolism.     

Effects of 24 Months of Growth Hormone (GH) Treatment on Serum Carboxylated and Undercarboxylated Osteocalcin Levels in GH-Deficient Adults

We studied the effect of growth hormone (GH) replacement on bone mineral density (BMD) and some parameters of bone metabolism, including undercarboxylated osteocalcin (ucOC), an independent predictive marker of fracture risk, which has not been previously determined or compared during GH treatment. Measurements were performed at baseline and after 6, 12, 18 and 24 months of the initiation of the GH therapy in 21 adult patients with GH deficiency. Significant increases were observed in BMD after 1 year at the lumbar spine and after 1.5 years at the femoral neck. Serum total OC and carboxylated (c) OC increased and reached the maximum at 6 months, but the values remained over the baseline at both 12 and 18 months. The ucOC:total OC ratio changed contrarily: it decreased at 6 months, then increased again and reached the baseline level during the next 18 months. Serum calcium (Ca), phosphate (P) and total alkaline phosphatase (ALP) levels increased after 6 months, thereafter the Ca and P values decreased, while the total ALP remained elevated until 12 months. Serum parathormone decreased at 12 months and increased again thereafter. GH replacement therapy is associated with improvement of ucOC, a marker of fracture risk, which in addition to the increase of BMD, might contribute to the beneficial effect of GH replacement therapy on bone metabolism.