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。     

Effects of nicotine on bone mass and strength in aged female rats.

This study investigated the effects of nicotine on bone mass and biomechanical properties in aged, estrogen-replete (sham-operated) and estrogen-deplete (ovariectomized) female rats. Eight month old, retired breeder, sham-operated and ovariectomized Sprague-Dawley rats were left untreated for 12 weeks to establish cancellous osteopenia in the ovariectomized group. The animals were then administered saline, low dose nicotine (6.0 mg/kg/day) or high dose nicotine (9.0 mg/kg/day) via osmotic minipumps for 12 weeks. Vertebrae and femora were collected at necropsy for determination of bone mass and strength. As expected, ovariectomy had a negative effect on most endpoints evaluated. Vertebral body bone mineral content (BMC) and density (BMD) and the structural (ultimate load and yield load) and material (ultimate stress, yield stress, and flexural modulus of elasticity) strength properties were lower in the OVX rats than in the sham-operated rats. Femoral diaphysis BMC, BMD, ultimate load, and flexural modulus were also lower in the OVX rats than in the sham-operated rats. The nicotine doses administered resulted in serum nicotine levels that averaged 1.5-4.5-fold greater than those observed in heavy smokers. Despite the high doses used, nicotine had no effect on vertebral BMC, BMD, or any of the structural and material strength properties in either the OVX or the Sham rats. In addition, nicotine had no effect on femoral diaphysis BMC, BMD, ultimate load, stiffness, ultimate stress, or flexural modulus. Femoral yield load and stress were lower in low dose nicotine-treated rats than in vehicle-treated rats. However, differences were not detected between the high dose nicotine- and vehicle-treated rats for either femoral yield load or stress. The results suggest that tobacco agents other than nicotine are responsible for the decreased bone density and increased fracture risk as observed in smokers.     

Age-related changes in bone mineral content and density in intact male F344 rats.

This study was undertaken to determine whether age-related bone loss occurs in intact male F344 rats. Bone loss was assessed in male F344 rats aged 3 to 27 months by scanning different bones using peripheral quantitative computed tomography (pQCT) densitometry. Cancellous and cortical bones were analyzed at the vertebra, proximal tibial metaphysis (PTM), and the neck of the femur. Cortical bone was also analyzed at the tibial and femoral diaphysis and at the tibio-fibula junction. In the vertebra, cancellous bone mineral content (Cn. BMC) did not change significantly with age. Cancellous bone mineral density (Cn. BMD) gradually decreased from 9 months onwards; and at 27 months of age, there was a 29% (p < 0.0001) decrease, when compared with 9-month-old animals. No significant change was observed in cortical bone mineral content (Ct. BMC) and cortical bone mineral density (Ct. BMD) with age. In the PTM, bone loss started to occur after 18 months of age. At 27 months of age, Cn. BMC decreased by 58% (p < 0.0001) and Cn. BMD also decreased by 58% (p < 0.0001). Ct. BMC decreased by 28% (p < 0.0001) in 27-month-old animals, whereas Ct. BMD was not affected by aging. At the tibio-fibula junction, Ct. BMC and Ct. BMD decreased after 18 months of age. At 27 months, Ct. BMC and Ct. BMD had decreased by 8% (p < 0.001) and 3% (p < 0.0001), respectively. Ct. BMC in the tibial diaphysis did not change significantly with age, whereas Ct. BMD decreased by 1% (p < 0.05) at 27 months. In the neck of the femur, Cn. BMC increased up to 24 months of age. Cn. BMD increased up to 18 months of age and decreased by 9% (p < 0.05) at 24 months and 11% (p < 0.001) at 27 months of age when compared with 18-month-old animals. Ct. BMC and Ct. BMD increased with age. In conclusion, although some components of the PTM decreased appreciably with age, in this study, most of the bone parameters analyzed either increased or did not change significantly with age. We conclude that unlike male Sprague Dawley rats, male F344 rats appear not to be a good model for studying age-related bone loss as occurs in aging men.     

Resveratrol supplementation preserves long bone mass,microstructure, and strength in hindlimb-suspended old male rats

Resveratrol has gained popularity as an “anti-aging” compound due to its antioxidant and anti-inflammatory properties. Few studies have investigated the role of resveratrol supplementation in the prevention of age-related bone loss and skeletal disuse despite increased inactivity and age-related bone loss in the elderly. The objective of the study was to investigate the effect of resveratrol supplementation on disuse and age-related bone loss. Old (age 33 months) Fischer 344 × Brown Norway male rats were provided either trans-resveratrol (12.5 mg/kg bw/day) or deionized distilled water by oral gavage for 21 days. Rats were hindlimb-suspended (HLS) or kept ambulatory (AMB) for 14 days. Both femora and tibiae were collected. Bone mass was measured by dual-energy X-ray absorptiometry and bone microstructure was determined by micro-computed tomography. HLS of old male rats accelerated loss of bone mineral content, decreased trabecular bone volume per unit of total volume, and increased trabecular separation. Resveratrol supplementation ameliorated bone demineralization and loss of bone microarchitecture in HLS old male rats. The peak force measured by the three-point bending test was reduced (P = 0.007) in HLS/control compared to AMB/control rats. Resveratrol supplementation ameliorated HLS-induced loss of femur strength. Plasma osteocalcin and alkaline phosphatase was higher (P < 0.04) and C-reactive protein was lower (P = 0.04) in old male rats given resveratrol. The bone protective effects of resveratrol appeared to be mediated through increased osteoblast bone formation, possibly due to reduced inflammation. Based on the results, resveratrol supplementation appeared to provide a feasible dietary therapy for preserving the skeletal system during disuse and age-related bone loss.     

Sex- and age-related changes in bone and serum osteocalcin

Summary We measured bone osteocalcin concentrations in EDTA extracts from iliac crest cortical bone specimens obtained postmortem from 63 men and 71 women (age range 19–90 years), and serum osteocalcin levels in healthy blood donors, 49 men and 49 women (age range 21–65 years). Bone and serum osteocalcin concentrations were higher in men than in women, and an age-related decline was observed in both sexes. In women, however, a temporary increase in serum (P<0.05) osteocalcin was seen in the sixth decade. This study shows sex- and age-related changes in bone osteocalcin consistent with changes in serum osteocalcin, confirming that serum measurement of osteocalcin reflects bone levels. As osteocalcin reflects osteoblastic activity and thus bone formation, the overall decline in bone and serum osteocalcin in men and women, and the increase in serum osteocalcin in the sixth decade in women, indicate that aging is associated with a decrease in bone formation and turnover and that osteoblastic activity and bone turnover are stimulated at the menopause.     

Activin increases bone mass and mechanical strength of lumbar vertebrae in aged ovariectomized rats

Activin is a member of the transforming growth factor-beta superfamily and is thought to be involved in the regulation of bone formation due to its presence in bone tissue and its osteogenic activity both in vitro and in vivo. We recently found that systemic administration of activin increased both tibial bone mass and mechanical strength in young growing rats. The present study investigated the effects of activin in aged ovariectomized (ovx) rats. Twelve-month-old Fischer rats were ovariectomized and maintained for 10 months. Recombinant human activin A (activin) or human parathyroid hormone 1-34 (PTH) was administered intramuscularly three times a week for 12 weeks. Activin (1 and 5 microg/kg) markedly increased lumbar vertebral bone mineral content and bone mineral density. Activin also increased the mechanical strength of the vertebral body, which was highly correlated to the bone mineral density of the vertebral body. The maximal response in bone mass and strength was observed at 1 microg/kg of activin, which was approximately equal to that induced by PTH at 40 microg/kg. Peripheral quantitative computed tomography revealed that activin enlarged the cross-sectional size of the vertebrae without changing the foramen area, indicating its effects on cortical shells. Histomorphometric analysis of cancellous bone of vertebral body in similar experiment showed that activin (3 microg/kg) increased bone volume and the mineralizing surface, although its effects were less than PTH. The present results indicate that low doses of activin are effective against vertebral bone loss in aged ovx rats.     

Thyroid-stimulating hormone restores bone volume, microarchitecture, and strength in aged ovariectomized rats.

We show the systemic administration of low levels of TSH increases bone volume and improves bone microarchitecture and strength in aged OVX rats. TSH's actions are mediated by its inhibitory effects on RANKL-induced osteoclast formation and bone resorption coupled with stimulatory effects on osteoblast differentiation and bone formation, suggesting TSH directly affects bone remodeling in vivo. INTRODUCTION: Thyroid-stimulating hormone (TSH) receptor haploinsufficient mice with normal circulating thyroid hormone levels have reduced bone mass, suggesting that TSH directly affects bone remodeling. We examined whether systemic TSH administration restored bone volume in aged ovariectomized (OVX) rats and influenced osteoclast formation and osteoblast differentiation in vitro. MATERIALS AND METHODS: Sprague-Dawley rats were OVX at 6 months, and TSH therapy was started immediately after surgery (prevention mode; n = 80) or 7 mo later (restoration mode; n = 152). Hind limbs and lumbar spine BMD was measured at 2- or 4-wk intervals in vivo and ex vivo on termination at 8-16 wk. Long bones were subjected to microCT, histomorphometric, and biomechanical analyses. The direct effect of TSH was examined in osteoclast and osteoblast progenitor cultures and established rat osteosarcoma-derived osteoblastic cells. Data were analyzed by ANOVA Dunnett test. RESULTS: In the prevention mode, low doses (0.1 and 0.3 microg) of native rat TSH prevented the progressive bone loss, and importantly, did not increase serum triiodothyroxine (T3) and thyroxine (T4) levels in aged OVX rats. In restoration mode, animals receiving 0.1 and 0.3 microg TSH had increased BMD (10-11%), trabecular bone volume (100-130%), trabecular number (25-40%), trabecular thickness (45-60%), cortical thickness (5-16%), mineral apposition and bone formation rate (200-300%), and enhanced mechanical strength of the femur (51-60%) compared with control OVX rats. In vitro studies suggest that TSH's action is mediated by its inhibitory effects on RANKL-induced osteoclast formation, as shown in hematopoietic stem cells cultivated from TSH-treated OVX rats. TSH also stimulates osteoblast differentiation, as shown by effects on alkaline phosphatase activity, osteocalcin expression, and mineralization rate. CONCLUSIONS: These results show for the first time that systemically administered TSH prevents bone loss and restores bone mass in aged OVX rats through both antiresorptive and anabolic effects on bone remodeling.     

牛磺酸治疗通过激活自噬介导对老年大鼠骨量和骨强度的保护作用

目的探讨牛磺酸(NHS)对老年大鼠骨量流失的影响,并探讨可能的机制。方法将30只大鼠随机分为对照组(CON)、模型组(MOD)以及牛磺酸组(NHS),每组10只;其中NHS组大鼠每天接受牛磺酸(2 g/kg)治疗12周;待治疗结束后通过Micro-CT检测、HE染色切片、血清指标、蛋白质印迹观察治疗效果,探讨可能的机制。结果治疗12周后,与MOD组相比,三点弯曲试验、Micro-CT和HE染色切片结果显示NHS组大鼠的骨小梁数量、骨强度和骨密度(bone mineral density,BMD)得到明显改善。NHS组大鼠最大载荷和弹性模量、BMD、TV/BV、Tb.N、Tb.Th和Tb.Sp较OVX组明显改善(P<0.05)。和MOD组比较,NHS治疗后大鼠血清BLAP、P1NP、TRACP-5b和β-CTX水平明显降低,组间差异有统计学意义(P<0.05)。和MOD组比较,NHS组Runx2、BMP2、Beclin-1和LC3Ⅱ/LC3-Ⅰ表达水平明显上调,而P62表达水平显著下调,比较差异有统计学意义(P<0.05)。结论NHS可能通过激活自噬,从而对年龄引起的骨量丢失起到保护作用。     

A nonprostanoid EP4 receptor selective prostaglandin E2 agonist restores bone mass and strength in aged, ovariectomized rats.

CP432 is a newly discovered, nonprostanoid EP4 receptor selective prostaglandin E2 agonist. CP432 stimulates trabecular and cortical bone formation and restores bone mass and bone strength in aged ovariectomized rats with established osteopenia. INTRODUCTION: The purpose of this study was to determine whether a newly discovered, nonprostanoid EP4 receptor selective prostaglandin E2 (PGE2) agonist, CP432, could produce bone anabolic effects in aged, ovariectomized (OVX) rats with established osteopenia. MATERIALS AND METHODS: CP432 at 0.3, 1, or 3 mg/kg/day was given for 6 weeks by subcutaneous injection to 12-month-old rats that had been OVX for 8.5 months. The effects on bone mass, bone formation, bone resorption, and bone strength were determined. RESULTS: Total femoral BMD increased significantly in OVX rats treated with CP432 at all doses. CP432 completely restored trabecular bone volume of the third lumbar vertebral body accompanied with a dose-dependent decrease in osteoclast number and osteoclast surface and a dose-dependent increase in mineralizing surface, mineral apposition rate, and bone formation rate-tissue reference in OVX rats. CP432 at 1 and 3 mg/kg/day significantly increased total tissue area, cortical bone area, and periosteal and endocortical bone formation in the tibial shafts compared with both sham and OVX controls. CP432 at all doses significantly and dose-dependently increased ultimate strength in the fifth lumber vertebral body compared with both sham and OVX controls. At 1 and 3 mg/kg/day, CP432 significantly increased maximal load in a three-point bending test of femoral shaft compared with both sham and OVX controls. CONCLUSIONS: CP432 completely restored trabecular and cortical bone mass and strength in established osteopenic, aged OVX rats by stimulating bone formation and inhibiting bone resorption on trabecular and cortical surfaces.     

Evaluation of long-term sequential changes in bone mass and strength following withdrawal of incadronate disodium (YM175) in ovariectomized rats

We evaluated the long-term effects of withdrawal of a newer third-generation bisphosphonate, incadronate disodium (YM175), on both cancellous and cortical bone mass and strength in ovariectomized (OVX) rats. One hundred and sixty female SD rats at 13 weeks of age were randomized into four groups: sham-operated, OVX, and low- and high- YM (0.01 or 0.1 mg/kg s.c., three times a week after OVX). After 4 weeks of treatment with vehicle or incadronate disodium, rats from each group (n = 8) were killed at 0 (baseline), 3, 6, 9, and 12 months after the withdrawal of YM175. Histomorphometric studies of the proximal tibia revealed a dose-dependent decrease in OVX-induced bone turnover; cancellous bone volume was significantly higher in the YM groups compared with the OVX control group up to 6 months after withdrawal at low dose and up to 12 months after withdrawal at high dose. The low-dose group showed little effect on tibial diaphyseal cortical bone volume and width, while the high-dose group preserved both cortical parameters 12 months after withdrawal. Mechanical testing of femurs revealed that both metaphyseal and diaphyseal strengths were significantly higher at high dose compared with the OVX group until 12 months after withdrawal. These observations demonstrated that high-dose incadronate disodium preserved both cancellous and cortical bone mass and strength in OVX rats for 12 months after withdrawal of the agent. Received: July 7, 2000 / Accepted: October 3, 2000     

Characteristics of bone turnover, bone mass and bone strength in Spontaneously Diabetic Torii-Lepr fa rats

The Spontaneously Diabetic Torii-Lepr (fa) (SDT-fa/fa) rat is a new model of obese type 2 diabetes. The SDT-fa/fa rat shows obesity and hyperglycemia at a young age compared to the Spontaneously Diabetic Torii (SDT-+/+) rat; however, bone abnormalities in the SDT-fa/fa rat have not been investigated. The objective of the present study was to investigate the effects of obese type 2 diabetes on bone turnover, bone mass, and bone strength in the SDT-fa/fa rat. Sprague-Dawley rats were used as control animals, and SDT-+/+ rats were used as non-obese type 2 diabetic rats. Serum osteocalcin and urine deoxypyridinoline levels were decreased in SDT-fa/fa rats compared to control rats at a young age. SDT-fa/fa rats showed decreases in bone mineral density and bone mineral content of the whole tibia, and shortening of the tibia and femur compared to control and SDT-+/+ rats. Deterioration in bone geometrical properties of the femur midshaft such as cortical thickness and minimum moment of inertia, was observed in SDT-fa/fa rats compared to control and SDT-+/+ rats. Furthermore, trabecular bone volume of the distal femur was decreased in SDT-fa/fa rats compared to control rats. These negative effects on bone in SDT-fa/fa rats caused severe decreases in maximum load, stiffness, and energy absorption of the femur. In addition, serum levels of homocysteine, a candidate for bone fragility markers, were elevated in SDT-fa/fa rats compared to control and SDT-+/+ rats. In conclusion, the SDT-fa/fa rat may be a useful model to investigate bone abnormalities in obese type 2 diabetes.     

Parathyroid hormone monotherapy and cotherapy with antiresorptive agents restore vertebral bone mass and strength in aged ovariectomized rats

Previous studies have shown that parathyroid hormone (PTH) monotherapy and cotherapy with estrogen or risedronate augment vertebral bone mass and bone strength in young, ovariectomized (OVX) rats. The current study was designed to determine whether PTH has similar bone anabolic effects in aged OVX rats at a much later stage of estrogen depletion. Female Sprague Dawley rats were subjected to sham surgery or bilateral ovariectomy at three months of age and maintained untreated for one year after surgery to allow for the development of vertebral osteopenia in OVX rats. Groups of baseline control and OVX rats were sacrificed at the end of this pretreatment period. The remaining OVX rats were then treated for ten weeks with vehicle, antiresorptive agents alone (estrogen, risedronate, or calcitonin), or PTH alone. Other groups of OVX rats were treated concurrently with PTH and each of the antiresorptive agents. The first and fourth lumbar vertebral bodies were processed undecalcified for quantitative bone histomorphometry and biomechanical testing, respectively. As expected, bone mass and compressive strength were decreased in the lumbar vertebral body of baseline OVX rats compared to baseline control rats. This bone loss was associated with decreases in trabecular number and width and an increase in trabecular separation. Treatment with estrogen, risedronate, or calcitonin alone failed to reverse the changes in bone mass, structure, and strength induced by ovariectomy. In contrast, treatment of OVX rats with PTH alone restored vertebral cancellous bone volume and ash density to the level of vehicle-treated control rats and increased vertebral maximum load, stress, and normalized load to well above this level. The hormone significantly increased trabecular width, but not number, in the lumbar vertebral body of OVX rats. Concurrent treatments with PTH and the antiresorptive agents did not augment cancellous bone and biomechanical competence to a greater, or lesser, extent than treatment with PTH alone. Compressive strength correlated significantly with bone mass and trabecular width in the lumbar vertebral body. These results indicate that PTH completely restores lost bone mass and improves bone strength in the vertebral body of aged OVX rats with established osteopenia. With our previous study in younger OVX rats, the current study demonstrates that the anabolic effect of PTH is independent of age and the stage of estrogen depletion in the rat skeleton.     

Strontium ranelate improves bone resistance by increasing bone mass and improving architecture in intact female rats.

Strontium ranelate given to intact rats at doses up to 900 mg/kg/day increases bone resistance, cortical and trabecular bone volume, micro-architecture, bone mass, and total ALP activity, thus indicating a bone-forming activity and an improvement of overall bone tissue quality. INTRODUCTION: Various anti-osteoporotic agents are available for clinical use; however, there is still a need for drugs able to positively influence the coupling between bone formation and bone resorption to increase bone mass and bone strength. Strontium ranelate (PROTELOS), a new chemical entity containing stable strontium (Sr), was tested for its capacity to influence bone quality and quantity. MATERIALS AND METHODS: The long-term effects of strontium ranelate on bone were investigated in intact female rats treated with various doses of strontium ranelate (0, 225, 450, and 900 mg/kg/day) for 2 years. In a second series of experiments, the effects of 625 mg/kg/day were evaluated in intact male and female rats for the same period of time. Bone mineral mass and mechanical properties were evaluated at various skeletal sites (vertebra and femur), and bone tissue micro-architecture was evaluated by static histomorphometry at the tibio-fibular junction (cortical bone) and at the tibia metaphysis (trabecular bone). Plasma total alkaline phosphatase (ALP) activity and serum levels of insulin-like growth factor-I (IGF-I) were also assessed. RESULTS: In female rats treated with strontium ranelate over 2 years, dose-dependent increases of bone strength and bone mass of the vertebral body (containing a large proportion of trabecular bone) and of the midshaft femur (containing mainly cortical bone) were detected without change in bone stiffness. Similar effects were observed in males at the level of the vertebra. This increase in mechanical properties was associated with improvements of the micro-architecture as assessed by increases of trabecular and cortical bone volumes and trabecular number and thickness. Finally, plasma total ALP activity and IGF-I were also increased in treated animals, compatible with a bone-forming activity of strontium ranelate. CONCLUSION: A long-term treatment with strontium ranelate in intact rats is very safe for bone and improves bone resistance by increasing bone mass and improving architecture while maintaining bone stiffness.     

Effects of tower climbing exercise on bone mass, strength, and turnover in growing rats.

To determine the effects of tower climbing exercise on mass, strength, and local turnover of bone, 50 Sprague-Dawley rats, 10 weeks of age, were assigned to five groups: a baseline control and two groups of sedentary and exercise rats. Rats voluntarily climbed the 200-cm tower to drink water from the bottle set at the top of it. In 4 weeks, the trabecular bone formation rate (BFR/bone surface [BS]), bone volume (BV/TV), and trabecular thickness (Tb.Th) of both the lumbar vertebra and tibia and the bone mineral density (BMD) of the tibia increased, while the osteoclast surface (Oc.S) decreased. The parameter values in the midfemur, such as the total cross-sectional area, the moment of inertia, the periosteal mineralizing surface (MS/BS), mineral apposition rate (MAR), BFR/BS, and bending load increased, while the endosteal MAR decreased. In 8 weeks, the increases in the bone mineral content (BMC), BMD of the femur and tibia, and the bending load values of the femur were significant, but the climbing exercise did not increase BMC, BMD, or the compression load of the lumbar vertebra. Although the periosteal MS/BS, MAR, and BFR/BS increased, the endosteal MS/BS, MAR, and BFR/BS decreased. These results show that climbing exercise has a beneficial effect on the femoral cortex and tibia trabecular, rather than the vertebral trabecular. In the midfemur, effects on bone formation are site specific, supporting accelerated cortical drift by mechanical stimulation.     

Effects of h-PTH on cancellous bone mass, connectivity, and bone strength in ovariectomized rats with and without sciatic-neurectomy.

The purpose of this study was to determine whether h-PTH (1-34) treatment would recover cancellous bone connectivity and bone strength in ovariectomized (OVX) or ovariectomized and sciatic-neurectomized (OVX+NX) rats. Seven-month-old female Wistar rats were treated with h-PTH or vehicle (6.0 microg/kg, six times a week, subcutaneously) for four weeks beginning 4, 8, or 12 weeks after OVX or OVX+NX. These were compared to age-matched baseline and sham-operated groups. Right tibiae were used for bone histomorphometry and node-strut analysis, and left tibiae were used for mechanical testing. The bone formation rates in the OVX and OVX+NX rats treated with h-PTH were significantly higher than those in their baseline controls. h-PTH treatment increased the node numbers and failure energies in the OVX rats, compared to their baseline controls, at all time points. However, in the OVX+NX rats, the effects of h-PTH treatment on the node number and failure energy were observed only at four weeks after surgery, but not at eight weeks or 12 weeks after surgery. These results suggest that the lowest limit, at which trabecular connectivity and bone strength are able to be restored by h-PTH, occurred between four and eight weeks in OVX+NX rats, but not in OVX rats. h-PTH cannot recover trabecular connectivity and bone strength in advanced osteopenia.     

Ethanol and its effects on fracture healing and bone mass in male rats.

Operatively induced, standardized tibia fractures in 42 10-week-old male rats were fixed with intramedullary nails. 21 of the rats were fed liquid containing 15% ethanol. 5 weeks after inducing the fracture, the rats were killed and the total body bone mineral density (BMD) was analyzed with the DEXA technique, and the mechanical properties of the fractured and the unfractured tibiae as well as the ipsi- and contralateral femoral shaft and femoral neck were tested. The rats given a liquid containing 15% ethanol were found to have significantly lower total BMD and total calcium than the controls. We also found a significantly lower bending moment and bending stiffness both in the fractured and unfractured tibiae among rats fed on ethanol. The energy absorption until refracture was less in rats fed on ethanol. Posttraumatic osteopenia was present, as judged by the mechanical tests of the ipsilateral femoral shaft and the femoral neck in all animals. There was no difference in this respect between the animals fed on ethanol and the controls. We found that ethanol disturbs bone metabolism which reduces the mechanical properties of the tibiae and femora of rats, but the healing process of an induced tibial shaft fracture was not affected.     

维生素E治疗对老年雌性大鼠骨量、骨代谢以及自噬水平影响

目的 观察维生素E对老年雌性大鼠骨量、骨代谢作用及自噬水平的影响.方法 10只年轻雌性大鼠和20只老年雌性Sprague-Dawley大鼠被随机分为三组:对照组(10只年轻大鼠)、模型组(10只老年大鼠)和治疗组(10只老年大鼠).在实验过程中,治疗组接受维生素E治疗.治疗12周后,通过Micro-CT和HE切片染色检...     

Time-dependent changes in biochemical bone markers and serum cholesterol in ovariectomized rats: Effects of raloxifene HCl, tamoxifen, estrogen, and alendronate

Bone loss associated with postmenopausal osteoporosis can be reduced by treatment with antiresorptive agents such as estrogen or bisphosphonates. Whereas bisphosphonates primarily affect bone loss, estrogens have an advantage of also lowering serum cholesterol levels, although they have a detrimental effect in the uterus. Recently, raloxifene HCl, a selective estrogen receptor modulator (SERM), has been shown to decrease both bone loss and cholesterol levels without the negative uterine effects. These antiresorptive agents reduce bone turnover, which can be evaluated by measuring bone turnover markers. To compare the effects of estrogen, two SERMs (raloxifene HCl and tamoxifen), and alendronate, a bisphosphonate that inhibits bone loss by an estrogen-independent pathway, on metabolic bone markers and cholesterol levels, rats were ovariectomized 2 weeks prior to 3 weeks of daily oral treatment with raloxifene HCl (3 mg/kg), ethynyl estradiol (0.1 mg/kg), tamoxifen (3 mg/kg), or alendronate (3 mg/kg). Raloxifene HCl, tamoxifen, and ethynyl estradiol reduced serum cholesterol to levels below control values within 4 days after initiation of treatment, whereas alendronate had no effect. After 3 weeks of treatment, serum cholesterol values in ethynyl estradiol treated animals, although still below the control value, had risen 6.4-fold; raloxifene HCl and tamoxifen values rose by only 1.4–1.5-fold. Therefore, compared with estrogen, SERMs may have a longer-term suppressive effect on serum cholesterol. At 4 days of treatment, ovariectomized rats had a 1.4-fold increase in serum osteocalcin level compared with controls. Ethynyl estradiol lowered this level within 1 week of treatment by 18%, with a more pronounced reduction of 34% at 3 weeks. In contrast, raloxifene HCl, tamoxifen, or alendronate had very little effect after the first week (6% to 13% reduction), although there was an 18% to 25% reduction by 3 weeks. Urinary pyridinoline levels, elevated 1.4-fold in the ovariectomized rat compared with controls 2 weeks after surgery, were reduced to control values after 2 weeks of treatment with raloxifene HCl, ethynyl estradiol, tamoxifen, or alendronate. These data support the concept that estrogen, raloxifene HCI, tamoxifen, and alendronate inhibit bone loss in the ovariectomized animal by reducing bone resorption. The results also indicate that for treatment of postmenopausal osteoporosis, raloxifene HCl may have an advantage over the other antiresorptives studied in having both non-uterotrophic and hypocholesterolemic effects in addition to its ability to inhibit bone resorption.     

Parathyroid hormone (1–34) increases vertebral bone mass, compressive strength, and quality in old rats

Human parathyroid hormone 1–34 (PITH) exerts an anabolic effect on bone in younger rats. The aim of the present study was to examine the effect of PTH on vertebral bone in 2-year-old male rats. The rats were treated with daily injections of 15 nmol/kg PTH or vehicle (V) for 56 days. Tetracycline and calcein were injected on day 15 and day 40 of the treatment period, respectively. The PTH treatment did not influence the body weights of the rats, the volumes of whole vertebra, or the vertebral body heights. However, the PTH treatment induced profound changes in the bone structure. Histomorphometric analyses of the vertebral bodies (L-6) revealed an approximate doubling of the cancellous bone volume after PTH treatment from 24.6 ± 1.3% to 54.9 ± 2.0% (p < 0.001) as well as a doubling of the trabecular thickness while the bone surface/bone volume decreased by 60%. PTH treatment also increased bone formation as indicated by an increase in mineral apposition rate (from 0.42 ± 0.01 to 0.89 ± 0.01 μm/day, p < 0.01), increased mineralizing surface (from 7.8 ± 1.4 to 43.8 ± 1.9%, p < 0.01) and an increase in both volume-related and surface-related bone formation rates (5 and 11 times, respectively). The biomechanical properties were analyzed using standardized bone specimens from the vertebral bodies of L-4 by applying cranial-caudal compression in a materials testing machine. The PTH treatment induced a substantial increase in the strength of the vertebral body: ultimate load increased by 66%, ultimate stiffness by 47%, and energy absorption by 98%. The increase in vertebral body strength was also evident after normalizing the parameters to the cross sectional area and the ash content of the vertebral body specimens. PTH treatment increased ultimate stress from 26 ± 3 to 44 ± 3 N per mm² (p < 0.01) and increased ultimate load normalized to ash content per mm specimen height from 59 ± 4 to 72 ± 4 N (mm/mg) (p < 0.05). The PTH treatment induced an increase in dry defatted bone density and ash density of both the vertebral body specimen (L-4) and the whole vertebra (L-5). In conclusion, PTH showed a remarkable ability to stimulate bone formation in the vertebral body of old rats. Furthermore, the biomechanical analysis revealed an enhanced compressive bone strength, even after correction for the increased bone mass, indicating an improved bone quality after the PTH treatment.     

Reference intervals for serum total cholesterol, HDL cholesterol and non-HDL cholesterol in Batswana adults

Reference intervals of total cholesterol, HDL cholesterol and non-HDL cholesterol concentrations were determined on 309 blood donors from an urban and peri-urban population of Botswana. Using non-parametric methods to establish 2.5th and 97.5th percentiles of the distribution, the intervals were: total cholesterol 2.16 - 5.52 mmol/l; non-HDL cholesterol 1.22 - 4.48 mmol/l; and HDL cholesterol 0.67 - 1.65 mmol/l and 0.59 - 1.59 mmol/l for females and males, respectively.