白藜芦醇对酒精诱导雄性大鼠骨量减少和骨强度降低的保护作用

目的探索白藜芦醇对酒精诱导雄性大鼠骨量减少和骨强度降低的影响。方法 30只12周雄性大鼠随机分为对照组、模型组和治疗组3组,每组10只。模型组和治疗组大鼠给予0.4 mL/100 g的20%乙醇溶液,每周3次。治疗组接受白藜芦醇40 mg/kg治疗,每日一次,治疗为期12周。治疗结束时收集血清和股骨对治疗结果进行评价。结果治疗12周后,治疗组的股骨骨密度较模型组显著升高,差异有统计学意义(P0.05);Mircro-CT显示治疗组大鼠股骨干骺端较模型组具有更多骨小梁以及更佳的骨微观参数,差异有统计学意义(P0.05);生物力学结果显示治疗组股骨的极限载荷和峰值负荷较模型组显著升高,差异有统计学意义(P0.05);而血清检测结果表明治疗组的碱性磷酸酶和骨钙素较模型组明显降低,差异有统计学意义(P0.05)。结论白藜芦醇对酒精诱导雄性大鼠骨量减少和骨强度降低有一定的保护作用。     

Lycopene treatment against loss of bone mass,microarchitecture and strength in relation to regulatory mechanisms in a postmenopausal osteoporosis model

Lycopene supplementation decreases oxidative stress and exhibits beneficial effects on bone health, but the mechanisms through which it alters bone metabolism in vivo remain unclear. The present study aims to evaluate the effects of lycopene treatment on postmenopausal osteoporosis. Six-month-old female Wistar rats (n = 264) were sham-operated (SHAM) or ovariectomized (OVX). The SHAM group received oral vehicle only and the OVX rats were randomized into five groups receiving oral daily lycopene treatment (mg/kg body weight per day): 0 OVX (control), 15 OVX, 30 OVX, and 45 OVX, and one group receiving alendronate (ALN) (2 μg/kg body weight per day), for 12 weeks. Bone densitometry measurements, bone turnover markers, biomechanical testing, and histomorphometric analysis were conducted. Micro computed tomography was also used to evaluate changes in microarchitecture. Lycopene treatment suppressed the OVX-induced increase in bone turnover, as indicated by changes in biomarkers of bone metabolism: serum osteocalcin (s-OC), serum N-terminal propeptide of type 1 collagen (s-PINP), serum crosslinked carboxyterminal telopeptides (s-CTX-1), and urinary deoxypyridinoline (u-DPD). Significant improvement in OVX-induced loss of bone mass, bone strength, and microarchitectural deterioration was observed in lycopene-treated OVX animals. These effects were observed mainly at sites rich in trabecular bone, with less effect in cortical bone. Lycopene treatment down-regulated osteoclast differentiation concurrent with up-regulating osteoblast together with glutathione peroxidase (GPx) catalase (CAT) and superoxide dismutase (SOD) activities. These findings demonstrate that lycopene treatment in OVX rats primarily suppressed bone turnover to restore bone strength and microarchitecture.     

Relation of axial bone mass to habitual calcium intake and to cortical bone loss in healthy early postmenopausal women

A group of 60 healthy early postmenopausal women participating in an ongoing study on the effect of habitual calcium intake on the rate of cortical bone loss at the radius, were subjected to additional skeletal measurements at the lumbar spine and femoral neck. The women were between 58 and 64 years of age, and 3 to 10 years postmenopausal. No correlations were found between habitual calcium intake (range 560 to 2580 mg/day) and either bone mineral content of the radius, the lumbar spine and the femoral neck, or spine deformity index. Body mass index was found to be positively correlated with bone mass indices of the radius (decrease of BMD and BMD) and femoral neck (BMC), but not with of the lumbar spine (BMC, BMD and SDI), even after adjustments had been made for confounding factors. Although the rate of cortical bone loss at the radius correlated significantly with bone mineral content of lumbar spine and femoral neck, the error in predicting bone mass of the lumbar spine or the femoral neck from longitudinal measurements of cortical bone at the radius was high. The rate of cortical bone loss did not correlate with the spine deformity index. We conclude that in healthy women in early menopause, the bone mineral content of both the appendicular and the axial skeleton are not influenced by habitual calcium intake. A higher body mass index has a protective effect on the appendicular skeleton but appears to be less protective to the axial skeleton. Longitudinal measurements of cortical bone mass are of limited value to predict bone density of the appendicular and axial skeleton.     

Treatment with intermittent calcitriol and calcium reduces bone loss after renal transplantation

BACKGROUND: Bone loss occurs during the first 6 months after renal transplantation (RT), and corticosteroid therapy plays an important role. Although calcium plus vitamin D administration prevents corticosteroid-induced osteoporosis, its use in RT recipients is limited by the risk of hypercalcemia. METHODS: This double-blind, randomized, and controlled prospective intervention trial examined the effect of intermittent calcitriol (0.5 microg/48 h) during the first 3 months after RT, plus oral calcium supplementation (0.5 g/day) during 1 year with calcium supplementation alone. The primary outcome measure was the change in bone mineral density (BMD) at 3 and 12 months after RT; we also explored whether the effect of calcitriol on BMD was different among vitamin D receptor (VDR) genotypes (BsmI). Forty-five recipients were randomized to calcitriol therapy (CT) and 41 were randomized to placebo (PL). RESULTS: Both groups had a similar degree of pre-existing hyperparathyroidism (197 +/- 229 vs. 191 +/- 183 pg/mL), but a more pronounced decrease of parathyroid hormone (PTH) levels after RT was observed in CT patients (at 3 months: 61.4 +/- 42.2 vs. 85.7 +/- 53.1 pg/mL, P= 0.02; at 12 months: 67.3 +/- 33.7 vs. 82.6 +/- 37 pg/mL; P= 0.08). CT patients preserved their BMD at the total hip significantly better than those on PL (3 months: 0.04 +/- 3.3 vs. -1.93 +/- 3.2%, P= 0.01; 12 months: 0.32 +/- 4.8 vs. -2.17 +/- 4.4%, P= 0.03); significant differences were noted at the intertrochanter, trochanter, and Ward's triangle. Differences did not reach significance at the femoral neck. Two CT patients (4.4%) and 4 PL patients (9.8%) developed a hypercalcemic episode during the first 3 months after RT. The effect of CT on BMD at 3 months was more prominent in recipients with the at-risk allele of the VDR gene (P= 0.03). CONCLUSION: Therapy with low-dose calcium supplements during 1 year, plus intermittent calcitriol for 3 months after RT, is safe, decreases PTH levels more rapidly, and prevents bone loss at the proximal femur; a more pronounced effect is seen in recipients with at least one at-risk allele of the VDR genotype.     

The effects of clodronate on increased bone turnover and bone loss due to ovariectomy in rats

The present study was carried out to investigate the ability of clodronate to inhibit ovariectomy-induced bone loss and increased bone turnover in rats. Estradiol was administered as a reference compound. Seventy Sprague-Dawley rats were ovariectomized (OVX) or sham-operated (Sham) at the age of 90 days and divided into seven groups. Two Sham and two OVX groups received subcutaneously either the vehicle of clodronate or the vehicle of estradiol. Other OVX groups were given s.c. either disodium clodronate at two dose levels (5 mg/kg or 12.5 mg/kg twice a week) or 17β-estradiol (10 μg/kg five times a week) for 8 weeks. Femur length, volume, dry weight, and ash weight were determined, and proximal ends of tibiae were used for bone histomorphometry. Markers of bone metabolism were measured from urine and serum. A significant loss of 54% of trabecular bone area of proximal tibial metaphysis was found at 8 weeks after ovariectomy. Clodronate and estradiol inhibited (p < 0.001) this osteopenia. Both drugs prevented the decrease in ash weight/volume of the femur. The inhibitory effect of clodronate and estradiol on bone resorption in OVX rats could be detected also in decreased urinary excretion of hydroxyproline and lysylpyridinoline (p < 0.001). Clodronate and estradiol decreased (p < 0.001) the ovariectomy-induced enhanced tibial endocortical mineral apposition rate (Ec.MAR) on the lateral cortex to the level of the Sham group. In contrast, periosteal MAR analyzed on the medial side of tibial cortical bone did not change significantly in the OVX/Veh group. Estradiol decreased periosteal MAR to below the level in the Sham group (p < 0.01). These results suggest that ovariectomy of growing rats resulted in tibial and femoral osteopenia two months later. Clodronate as well as estradiol can suppress bone resorption and turnover in ovariectomized rats, inhibiting the development of osteopenia. Both clodronate doses (5 and 12.5 mg/kg) had beneficial effects in ovariectomized animals.     

Progression of vascular calcifications is associated with greater bone loss and increased bone fractures

SUMMARY: In this prospective study, we found a positive relationship between the prevalence of aortic calcifications and age. Aortic calcifications at baseline were positively associated with osteoporotic fractures. In addition, progression of aortic calcifications was also positively associated with the rate of decline in BMD at lumbar spine. INTRODUCTION: The aim of this study was to analyze the relationship between the progression of abdominal aortic calcification and osteoporosis in a Spanish cohort of men and women older than 50. METHODS: Men and women (n=624) aged 50 and over underwent two lateral X-rays of thoracic and lumbar spine and a dual X-ray absorptiometry (DXA) study at lumbar spine and hip, and were followed during 4 years. Abdominal aortic calcifications were classified as absent, mild-moderate and severe. RESULTS: There was a positive relationship between the prevalence of aortic calcifications and age. In both sexes, prevalent severe aortic calcifications were positively associated with prevalent osteoporotic fractures [odds ratio (OR)=1.93 (1.02-3.65)]. The association was stronger when only vertebral fracture was considered [OR=2.45 (1.23-4.87)]. In addition, progression of aortic calcifications showed a positive association with the rate of decline in bone mineral density (BMD) at lumbar spine. CONCLUSIONS: Aortic calcifications at baseline were positively associated with osteoporotic fractures. The progression of aortic calcifications was also positively associated with the rate of decline in BMD at lumbar spine.     

大豆异黄酮对肾辐射损伤大鼠骨量和骨结构的影响

目的观察大豆异黄酮对肾辐射损伤大鼠骨量、骨生物力学和骨形态计量的影响.方法应用15Gy 137Cs γ射线局部照射大鼠双侧肾脏,建立肾损伤引起继发性骨质疏松模型,以假照射组大鼠为对照.术后7 d开始用药,给予大豆异黄酮(100 mg/kg·d),以萌格旺(0.1 μg/kg·d)为阳性对照药物,治疗3个月后处死大鼠,观察骨量、骨生物力学和骨形态计量学指标改变,综合评价大豆异黄酮对肾辐射损伤性骨质疏松的防治作用.结果肾辐射损伤大鼠骨量、骨生物力学指标较假照射组显著降低(P＜0.05),表明肾辐射损伤引起大鼠继发性骨质疏松模型成功;大豆异黄酮治疗能明显增加模型大鼠的腰椎BMD、股骨干重与灰重,提高股骨三点弯曲最大载荷,增加腰椎骨小梁面积百分比(P＜0.05).结论大豆异黄酮对肾局部辐射损伤诱导骨质疏松模型大鼠的骨量和骨结构有明显改善作用.     

Discordance between bone turnover and bone loss: effects of aging and ovariectomy in the rat.

Mechanical strain maintains bone architecture even under conditions of increased bone turnover such as occurs with ovarian hormone deficiency. The rat distal femur contains two sites that apparently experience different levels of mechanical strain and therefore the rat is a suitable model for investigating such effects. The femoral epiphysis experiences higher strain energy compared with the metaphysis and we report the effects of aging between 7 and 12 months and the postovariectomy effects over the same time period on cancellous bone variables measured at these two sites. Age-related bone loss in sham-operated (Sham) animals occurred in both regions, with a greater fall in the metaphysis than in the epiphysis (trabecular bone volume [BV/TV, %] Mean [SEM] Metaphysis: day 0, 25. 9 [2.4]; day 150, 8.8 [1.3]: Epiphysis: day 0, 44.8 [1.7]; day 150, 36.7 [1.4] [p < 0.0001]). With ovariectomy (OVX) there was a 73% reduction in cancellous bone at the metaphysis compared with no specific loss at the epiphysis (BV/TV [%] OVX: Metaphysis: day 150, 2.4 [0.4] [p < 0.01 compared with Sham]: Epiphysis: day 150 29.3 [2. 7] [NS]). Osteoblast cell activity and osteoclast surface were increased after ovariectomy in both regions. The mineral apposition rate decreased at 9.5 months of age in both regions (p < 0.0001), independent of ovariectomy, and was coincident with a reduction in trabecular number in the epiphyses of both operative groups and in the metaphysis of the ovary-intact group. These data suggest that local mechanical strain governs bone balance with aging and that architectural changes resulting from age-related bone loss may mirror those following estrogen deficiency but occur via a different cellular mechanism.     

Shock wave treatment shows dose-dependent enhancement of bone mass and bone strength after fracture of the femur

Shock wave treatment is believed to improve bone healing after fracture. The purpose of this study was to evaluate the effect of shock wave treatment on bone mass and bone strength after fracture of the femur in a rabbit model. A standardized closed fracture of the right femur was created with a three-point bending method in 24 New Zealand white rabbits. Animals were randomly divided into three groups: (1) control (no shock wave treatment), (2) low-energy (shock wave treatment at 0.18 mJ/mm2 energy flux density with 2000 impulses), and (3) high-energy (shock wave treatment at 0.47 mJ/mm2 energy flux density with 4000 impulses). Bone mass (bone mineral density (BMD), callus formation, ash and calcium contents) and bone strength (peak load, peak stress and modulus of elasticity) were assessed at 12 and 24 weeks after shock wave treatment. While the BMD values of the high-energy group were significantly higher than the control group (P = 0.021), the BMD values between the low-energy and control groups were not statistically significant (P = 0.358). The high-energy group showed significantly more callus formation (P < 0.001), higher ash content (P < 0.001) and calcium content (P = 0.003) than the control and low-energy groups. With regard to bone strength, the high-energy group showed significantly higher peak load (P = 0.012), peak stress (P = 0.015) and modulus of elasticity (P = 0.011) than the low-energy and control groups. Overall, the effect of shock wave treatment on bone mass and bone strength appears to be dose dependent in acute fracture healing in rabbits.     

Daidzein together with high calcium preserve bone mass and biomechanical strength at multiple sites in ovariectomized mice

As the prevalence of osteoporosis is increasing, and the adverse effects of hormone replacement therapy are evident, women are searching for natural alternatives such as soy isoflavones to help prevent postmenopausal osteoporosis. Daidzein is one of the most abundant isoflavones present in soy and it is unique as it can be further metabolized to equol, a compound with greater estrogenic activity than other isoflavones. The objective of this study was to determine the effects of purified daidzein in combination with high calcium (Ca) on preserving femur and lumbar vertebrae (LV1-LV4) bone mineral density (BMD) and biomechanical bone strength at three different sites (femur midpoint, femur neck and LV3) in ovariectomized mice. Sham (SH) mice (n = 12) received control diet (AIN93G) containing 2 g Ca/kg diet and ovariectomized mice were randomized to 1 of 6 groups (n = 12/group): OVX (2 g Ca/kg diet), HCa (25 g Ca/kg diet), HD (2 g Ca + 200 mg daidzein/kg diet), HDCa (25 g Ca + 200 mg daidzein/kg diet), LD (2 g Ca + 100 mg daidzein/kg diet) or LDCa (25 g Ca + 100 mg daidzein/kg diet) for 12 weeks. HDCa preserved femur and vertebrae BMD and biomechanical bone strength (at all three sites) compared to the OVX group, however, only femur yield load (at midpoint) was preserved to a level that was greater (P < 0.05) than HCa alone. Mice fed HD diet had greater (P < 0.05) femur BMD than OVX group, however, daidzein alone (HD) did not appear to preserve trabecular bone (i.e., vertebrae BMD and vertebra peak load). All mice fed daidzein produced equol and there were no uterotrophic effects of daidzein at either dose. Both daidzein and Ca attenuated the increase in serum IL-1beta observed in the OVX group. The results from this study suggest that the combination of daidzein and high Ca favorably affect cortical and trabecular bone as indicated by femur and lumbar vertebrae BMD and biomechanical strength but much of this effect is mediated by the high Ca diet. Further investigation is required to determine optimal dietary levels of daidzein and Ca with the long-term goal of developing a dietary strategy to prevent postmenopausal osteoporosis and related fragility fractures.     

A multi-factorial analysis of bone morphology and fracture strength of rat femur in response to ovariectomy

Background

Postmenopausal osteoporosis develops due to a deficiency of estrogen that causes a decrease in bone mass and changes in the macro- and micro-architectural structure of the bone, leading to the loss of mechanical strength and an increased risk of fracture. Although the assessment of bone mineral density (BMD) has been widely used as a gold standard for diagnostic screening of bone fracture risks, it accounts for only a part of the variation in bone fragility; thus, it is necessary to consider other determinants of bone strength. Therefore, we aimed to comprehensively evaluate the architectural changes of the bone that influence bone fracture strength, together with the different sensitivities of cortical and trabecular bone in response to ovariectomy (OVX).

Methods

Bone morphology parameters were separately analyzed both in cortical and in trabecular bones, at distal-metaphysis, and mid-diaphysis of OVX rat femurs. Three-point bending test was performed at mid-diaphysis of the femurs. Correlation of OVX-induced changes of morphological parameters with breaking force was analyzed using Pearson’s correlation coefficient.

Results

OVX resulted in a decline in the bone volume of distal-metaphysis trabecular bone, but an increase in distal-metaphysis and mid-diaphysis cortical bone volume. Tissue mineral density (TMD) remained unchanged in both the trabecular and cortical bone of the distal metaphysis but decreased in cortical bone of the mid-diaphysis. The OVX significantly increased the breaking force at mid-diaphysis of the femurs.

Conclusions

OVX decreased the trabecular bone volume of the distal-metaphysis and increased the cortical bone volume of the distal-metaphysis and mid-diaphysis. Despite the reduction in TMD and increased cortical porosity, bone fracture strength increased in the mid-diaphysis after OVX. These results indicate that analyzing a single factor, i.e., BMD, is not sufficient to predict the absolute fracture risk of the bone, as OVX-induced bone response vary, depending on the bone type and location. Our results strongly support the necessity of analyzing bone micro-architecture and site specificity to clarify the true etiology of osteoporosis in a clinical setting.

     

Reductions in bone mass, structure, and strength in axial and appendicular skeletons associated with increased turnover after ovariectomy in mature cynomolgus monkeys and preventive effects of clodronate.

Over 16 months, we evaluated the effects of ovariectomy (OVX) and bisphosphonate clodronate (CLO) on bone in 48 cynomolgus monkeys (9-15 years old) fed a normal calcium diet. We established three OVX groups (oral CLO at 0 [OVX control], 12, or 60 mg/kg per day) and one sham-operated (SHAM) group. At 16 months, the bone mineral density (BMD) values (percentage of group baseline; OVX control vs. SHAM) for lumbar bone (L3-L5), proximal femur, midfemur, radius, and tibia were -2.6% versus 11.2%, -3.5% versus 8.9%, -3.0% versus 9.0%, -5.5% versus 15.7%, and -6.7% versus 13.9%, respectively. In OVX control (i) tibia showed significant loss of bone mineral content (BMC; vs. baseline), (ii) urinary deoxypyridinoline (DPD) and serum osteocalcin (OC) levels increased (peak = 182% and 168%, respectively, of SHAM), (iii) in lumbar bone and midfemur, ultimate load (UL) was reduced (vs. SHAM), (iv) in lumbar bone, trabecular bone-formation rates (BFRs) were not changed significantly, but tibial endocortical and intracortical bone formation rates were significantly raised (vs. SHAM), (v) the volumetric BMD (vBMD) and geometry of the tibial cortex (measured by peripheral quantitative computed tomography [pQCT]) were significantly reduced (vs. SHAM). CLO, 60 mg/kg per day but not 12 mg/kg per day, significantly inhibited OVX-induced changes, age-dependent increases in bone mass, and ability to maintain structure. Thus, in OVX mature cynomolgus monkeys (possibly, a unique model of the cortical bone loss secondary to estrogen deficiency), the post-OVX increases in systemic bone markers were slight, but stimulation of local turnover in the cortical envelope was enough to cause bone loss (more so in tibia than in lumbar trabecular bone). High-dose CLO prevented these changes.     

Effect of weight manipulation on bone loss due to ovariectomy and the protective effects of estrogen in the rat

Summary While characterizing the effects of estrogen on an ovariectomized (OVX) rat model of bone loss, we examined several weight-matching regimens e.g.,ad libitum (feed bins continually full), weight matched (rate of weight gain for OVX and Sham-OVX groups was equalized), and weight restricted (weight gain rates for all groups were equalized to that of estrogen-treated OVX rats) for possible effects. Bone loss following ovariectomy is primarily the result of an increase in bone resorption and is extremely sensitive to the effects of estrogens. Thus, in all of our analyses, treatment with 170-estradiol served as a positive control for the prevention of bone loss. Each weight-matching study had three groups: control (Sham-OVX), OVX, and OVX + 170 estradiol (0.1 mg/kg/day), and lasted for either 2, 4, or 6 weeks. Throughout the study, each Sprague Dawley rat was weighed every other day, and following sacrifice, a femur was removed for bone mineral density (BMD) analysis at the distal metaphysis by single photon absorptiometry. Following 2 weeks of dietary modifications, no significant differences were detected in BMD among thead lib or weight matched groups. However, an estradiol-preventable reduction in BMD in restricted OVX rats was detected at 2 weeks postovariectomy. Additionally, OVX rats in all three dietary regimens displayed an estrogen-preventable reduction in proximal femur BMD at 4 and 6 weeks postovariectomy. These results indicate that a 4-week rat ovariectomized model of bone loss, under conditions of ad libitum feeding, shows great potential for pharmacologic manipulation.     

Treatment with vitamin D and calcium reduces bone loss after renal transplantation: a randomized study

A decrease in bone mineral density (BMD) is a major complication of renal transplantation (RTx), predominantly occurring within the first 6 mo after RTx. The most important causative factor is the use of corticosteroids, but persisting hyperparathyroidism and abnormalities in vitamin D metabolism play a role too. This study examines the effect of treatment with calcium and active vitamin D on the loss of BMD in the first 6 mo after RTx. A total of 111 renal transplant recipients (65 men, 46 women; age, 47 +/- 13 yr) were randomized to either treatment with active vitamin D (0.25 microg/d) plus calcium (1000 mg/d) (CaD group), or to no treatment (NoT group). Immunosuppressive therapy consisted of cyclosporine, prednisone, and mycophenolate mofetil. Laboratory parameters and BMD (lumbar spine and hip) were measured at 0, 1 (laboratory only), 3, and 6 mo after RTx. Lumbar BMD was nearly normal at the time of RTx. In both groups, a significant decrease in lumbar BMD was observed during the first 3 mo (CaD, -3.3 +/- 4.3%; P < 0.0001; NoT, -4.1 +/- 4.8%; P < 0.0001). Between the third day and sixth month, lumbar BMD slightly recovered in the CaD group, but it decreased further in the NoT group (total loss 0 to 6 mo: CaD, -2.6 +/- 5.0% [P < 0.001]; NoT, -5.0 +/- 4.7% [P < 0.0001]). As a result, the amount of bone loss at 6 mo was significantly lower in the CaD group (P = 0.02). Loss of BMD at the different femoral sites was also significantly reduced in the CaD group. Apart from a trend toward more frequent hypercalcemia in the CaD group, no clinical or biochemical differences existed between the groups. Treatment with a low dose of active vitamin D and calcium partially prevents bone loss at the lumbar spine and proximal femur during the first 6 mo after RTx.     

Precompetitive and recreational gymnasts have greater bone density, mass, and estimated strength at the distal radius in young childhood

Summary  

Young recreational and precompetitive gymnasts had, on average, 23% greater bone strength at the wrist compared to children participating in other recreational sports. Recreational gymnastics involves learning basic movement patterns and general skill development and as such can easily be implemented into school physical education programs potentially impacting skeletal health.     

Less periprosthetic bone loss following the anterolateral approach to the hip compared with the direct lateral approach

Background and purpose — The loss of bone mineral in the proximal femur following hip arthroplasty may increase the fracture risk around uncemented stems. We hypothesized that the surgical approach to the hip might influence bone mineral changes around the femoral stem in patients with a femoral neck fracture (FNF).

Patients and methods — This was a pre-specified subgroup analysis (n = 51) of an ongoing randomized trial (n = 120) in patients with FNF. Participants were allocated to an uncemented hemiarthroplasty inserted through a direct lateral (Hardinge) approach or an anterolateral (modified Watson-Jones) approach. The 51 patients (mean age 83 (70–90) years, 33 women) were measured by dual-energy X-ray absorptiometry (DXA) to assess changes in periprosthetic bone mineral density (BMD).

Results — The mean change in total BMD differed between groups at 12 months in favor of the anterolateral group (4.8%, 95% CI 0.0–9.6; p = 0.05). DXA at 3 months displayed BMD loss in the proximal Gruen zones in the lateral group compared with the anterolateral group. Zone 1 (–5.0% vs. 2.7%), zone 2 (–4.3% vs. 4.1%), zone 6 (–6.5% vs. 0.0%) and zone 7 (–11% vs. –2.4%, all p < 0.05).

Interpretation — DXA measurements in this study indicate that surgical approach to the hip influences periprosthetic BMD. Clinical implications remain uncertain. Our conclusions should be interpreted with caution as we did not perform adjustments for multiple tests, possibly leading to inflation of false-positive findings.     

Effect of raloxifene combined with monofluorophosphate as compared with monofluorophosphate alone in postmenopausal women with low bone mass: a randomized,controlled trial

Raloxifene effectively reduces the incidence of vertebral fractures in patients with postmenopausal osteoporosis. Recent data suggest that low-dose monofluorophosphate (MFP) plus calcium reduces the vertebral fracture rate in postmenopausal women with moderate osteoporosis. The objective of this study was to evaluate the combination of raloxifene and MFP in the treatment of postmenopausal women with osteopenia, osteoporosis and severe osteoporosis. A total of 596 postmenopausal women with osteopenia, osteoporosis and severe osteoporosis (mean femoral neck T-score of –2.87 SD) were randomized to treatment with 60 mg/day raloxifene HCl and 20 mg/day fluoride ions (as MFP) or 20 mg/day fluoride and placebo for 18 months. All patients received calcium (1000 mg/day) and vitamin D (500 IU/day) supplements. Changes in bone mineral density (BMD), as primary endpoint, and the rate of osteoporotic fractures and biochemical markers, as secondary endpoints, were assessed. As compared with MFP, raloxifene plus MFP was associated with significantly greater mean increases in the BMD of the femoral neck (1.37% versus 0.33%; P=0.004), total hip (0.89% versus –0.42%; P<0.001) and lumbar spine (8.80% versus 5.47% P<0.001). In the raloxifene plus MFP group, 16 patients sustained 17 osteoporotic fractures, as compared with 22 patients sustaining 34 incident osteoporotic fractures in the MFP group (P=0.313). One patient in the raloxifene plus MFP group sustained multiple osteoporotic fractures, as compared with eight patients in the MFP group (P=0.020). MFP alone significantly increased the serum bone alkaline phosphatase (bone ALP) and the urinary C-terminal crosslinking telopeptide of type I collagene (U-CTX). The addition of raloxifene in the combination arm blunted the rise in bone ALP, which remained nevertheless significant, and abolished the increase in U-CTX. The combination of raloxifene with MFP was generally well tolerated. This study demonstrates that, in postmenopausal women with osteopenia, osteoporosis and severe osteoporosis, the combination therapy of raloxifene plus MFP favorably influences the BMD and the bone formation and resorption balance, and may reduce the risk of multiple osteoporotic fractures compared to MFP alone.     

Selective deletion of the membrane-bound colony stimulating factor 1 isoform leads to high bone mass but does not protect against estrogen-deficiency bone loss

To better define the biologic function of membrane-bound CSF1 (mCSF1) in vivo, we have generated mCSF1 knockout (k/o) mice. Spinal bone density (BMD) was 15.9% higher in k/o mice compared to wild-type (wt) controls (P < 0.01) and total BMD was increased by 6.8% (P < 0.05). A higher mean femur BMD was also observed but did not reach statistical significance (6.9% P = NS). The osteoclastogenic potential of bone marrow isolated from mCSF1 k/o mice was reduced compared to wt marrow. There were no defects in osteoblast number or function suggesting that the basis for the high bone mass phenotype was reduced resorption. In addition to a skeletal phenotype, k/o mice had significantly elevated serum triglyceride levels (123 ± 7 vs. 88 ± 3.2 mg/dl; k/o vs. wt, P < 0.001), while serum cholesterol levels were similar (122 ± 6 vs. 116 ± 6 mg/dl; k/o vs. wt, P = NS). One month after surgery, 5-month-old k/o and wt female mice experienced the same degree of bone loss following ovariectomy (OVX). OVX induced a significant fourfold increase in the expression of the soluble CSF1 isoform (sCSF1) in the bones of wt mice while expression of mCSF1 was unchanged. These findings indicate that mCSF1 is essential for normal bone remodeling since, in its absence, BMD is increased. Membrane-bound CSF1 does not appear to be required for estrogen-deficiency bone loss while in contrast; our data suggest that sCSF1 could play a key role in this pathologic process. The reasons why mCSF1 k/o mice have hypertriglyceridemia are currently under study.     

Human lactation: forearm trabecular bone loss, increased bone turnover, and renal conservation of calcium and inorganic phosphate with recovery of bone mass following weaning

The calcium (Ca) metabolism of established human lactation was studied in 40 adult women (mean age 32.4 years) who had been breast-feeding for 6 months (Lac) and in 40 age-matched controls (Con) using fasting urine and blood biochemistry and forearm single-photon bone mineral densitometry (BMD). Serial studies were performed up to 6 months after weaning in Lac women and repeated once in Con women. During lactation the significant findings were (1) a selective reduction (7.1%, P less than 0.03) in BMD at the ultradistal site containing 60% trabecular bone, but not at two more proximal, chiefly cortical bone sites; (2) increased bone turnover affecting bone resorption [fasting hydroxyproline excretion, Lac 2.22 +/- 0.12 mumol/liter GF (mean +/- SEM), Con 1.19 +/- 0.04, P less than 0.001] and affecting bone formation (plasma alkaline phosphatase, Lac 81.9 +/- 2.5 IU/liter, Con 53.5 +/- 2.7, P less than 0.001, and serum osteocalcin, Lac 14.0 +/- 0.7 microgram/liter, Con 7.3 +/- 0.4, P less than 0.001); and (3) renal conservation in the fasting state of both Ca and inorganic phosphate (Pi) with a resultant moderate increase in plasma Pi but not in plasma Ca (total or ionized). There were no differences between the groups in serum parathyroid hormone (PTH, intact and midmolecule assays), 25-hydroxy- and 1,25-dihydroxyvitamin D, nephrogenous cyclic AMP production, or plasma creatinine.(ABSTRACT TRUNCATED AT 250 WORDS)