The influence of dietary sodium on bone development in growing rats

The present study investigated the effects of dietary sodium on bone growth in young rats. Five-week-old rats were fed one of three different diets for 60 days: low sodium (NaCl, 0.32 g/kg diet), normal sodium (NaCl, 2.6 g/kg) and high sodium (NaCl, 20 g/kg). The proximal tibial metaphysis (PTM), the fifth lumbar vertebra (LV5) and the middle part of the tibia shaft (TX) were analysed by bone histomorphometry. The expression of three osteogenesis genes, Runx2, osteopontin and osteocalcin, was determined by RT-PCR in bone samples from the skull. In both the PTM and LV5, trabecular area and thickness were increased by the low-sodium diet, while the high-sodium diet decreased trabecular area in LV5. Dynamic data revealed that sodium restriction increased bone formation parameters in the PTM and LV5, but decreased bone resorption in LV5. In TX, endosteal bone formation was enhanced by the low-sodium diet and depressed by the high-sodium diet compared to the normal sodium group. But there were no statistically changes in the cortical bone area of TX. Low-sodium intake significantly enhanced the expression of all three osteogenesis genes compared to the normal sodium group, while high-sodium intake suppressed osteogenic gene expression. Our results suggest that sodium restriction in growing rats promotes bone development by influencing both bone formation and resorption.     

Simvastatin did not prevent nor restore ovariectomy-induced bone loss in adult rats

Current published results on whether statins have beneficial effects on bone metabolism have been conflicting so far. In order to further investigate if statins were promising candidates for the treatment for osteoporosis, we conducted a study in which rats were ovariectomized (OVX) at 6 months of age, allowed to lose bone for 60 days and followed by oral administration of simvastatin at the dose levels of 0.3-10 mg/kg/d for 60 days. PGE2 (6 mg/kg) was used as a positive control. Study endpoints included bone histomorphometry on the proximal tibial metaphysis (PTM) and the tibial diaphysis (TX), dual-energy X-ray absorptiometry on the right femur and micro computed tomography (ICT) on the 5th lumbar vertebra (LV). After 120 days of OVX, cancellous bone lost by 80% in the PTM and 18% in the LV accompanied by increased bone formation and resorption. Simvastatin at all dose levels did not affect bone volume, bone formation rate and bone erosion surface when compared to 120 day ovariectomized animals at all bone sites studied. By contrast, PGE2 restored cancellous and cortical bone area to sham control levels. In conclusion, this study demonstrated that unlike PGE2, oral administration of simvastatin did not have effects on cancellous or cortical bone formation and resorption; and consequently was not able to prevent further bone loss or restore bone mass in the osteopenic, OVX rats.     

杏仁中央核损毁对缺钠大鼠钠欲行为启动和表达的影响

目的:探讨杏仁中央核(CeA)损毁对缺钠大鼠钠欲行为启动和表达的影响。方法:将18只成年雄性SD大鼠随机分为3组(n=6):双侧Ce A损毁组、假损毁组和不损毁组,手术恢复后给予大鼠14 d低钠饲料摄食以建立缺钠大鼠模型,运用单笼双瓶选择测试方法观察缺钠大鼠在24 h内5个不同时间段对0.3 mol/L NaCl和自由饮水的摄入情况。应用免疫荧光化学染色方法观察杏仁中央核损毁与否对缺钠或正常大鼠孤束核内醛固酮敏感神经元活动的影响。结果:低钠饮食14 d后,大鼠对0.3 mol/L NaCl 24 h内饮用量和偏爱率比低钠饮食前明显增加(P<0.01);杏仁中央核损毁后缺钠大鼠对0.3 mol/L Na Cl溶液的摄入量和偏爱率显著下降(P<0.01)。杏仁中央核损毁对低钠饮食诱发的大鼠孤束核内醛固酮敏感神经元活动增加没有影响。结论:低钠饮食诱导大鼠钠欲行为表达增加;杏仁中央核损毁压抑缺钠大鼠钠欲行为的表达,而对缺钠大鼠的钠欲行为的启动没有影响。     

Differential effects of endothelin on activation of renal mechanosensory nerves: stimulatory in high-sodium diet and inhibitory in low-sodium diet

Activation of renal mechanosensory nerves is enhanced by high and suppressed by low sodium dietary intake. Afferent renal denervation results in salt-sensitive hypertension, suggesting that activation of the afferent renal nerves contributes to water and sodium balance. Another model of salt-sensitive hypertension is the endothelin B receptor (ETBR)-deficient rat. ET and its receptors are present in sensory nerves. Therefore, we examined whether ET receptor blockade altered the responsiveness of the renal sensory nerves. In anesthetized rats fed high-sodium diet, renal pelvic administration of the ETBR antagonist BQ-788 reduced the afferent renal nerve activity (ARNA) response to increasing renal pelvic pressure 7.5 mmHg from 26+/-3 to 9+/-3% and the PGE2-mediated renal pelvic release of substance P from 9+/-1 to 3+/-1 pg/min. Conversely, in rats fed low-sodium diet, renal pelvic administration of the ETAR antagonist BQ-123 enhanced the ARNA response to increased renal pelvic pressure from 9+/-2 to 23+/-6% and the PGE2-mediated renal pelvic release of substance P from 0+/-0 to 6+/-1 pg/min. Adding the ETAR antagonist to ETBR-blocked renal pelvises restored the responsiveness of renal sensory nerves in rats fed a high-sodium diet. Adding the ETBR antagonist to ETAR-blocked pelvises suppressed the responsiveness of the renal sensory nerves in rats fed a low-sodium diet. In conclusion, activation of ETBR and ETAR contributes to the enhanced and suppressed responsiveness of renal sensory nerves in conditions of high- and low-sodium dietary intake, respectively. Impaired renorenal reflexes may contribute to the salt-sensitive hypertension in the ETBR-deficient rat.     

Dietary zinc reduces osteoclast resorption activities and increases markers of osteoblast differentiation,matrix maturation,and mineralization in the long bones of growing rats

The nutritional influence of zinc on markers of bone extracellular matrix resorption and mineralization was investigated in growing rats. Thirty male weanling rats were randomly assigned to consume AIN-93G based diets containing 2.5, 5, 7.5, 15 or 30 μg Zn/g diet for 24 days. Femur zinc increased substantially as zinc increased from 5 to 15 μg/g diet and modestly between 15 and 30 μg/g (P<.05). By morphological assessment, trabecular bone increased steadily as dietary zinc increased to 30 μg/g. Increasing dietary zinc tended to decrease Zip2 expression nonsignificantly and elevated the relative expression of metallothionen-I at 15 but not 30 μg Zn/g diet. Femur osteoclastic resorption potential, indicated by matrix metalloproteinases (MMP-2 and MMP-9) and carbonic anhydrase-2 activities decreased with increasing dietary zinc. In contrast to indicators of extracellular matrix resorption, femur tartrate-resistant acid and alkaline phosphatase activities increased fourfold as dietary zinc increased from 2.5 to 30 μg Zn/g. Likewise, 15 or 30 μg Zn/g diet resulted in maximum relative expression of osteocalcin, without influencing expression of core-binding factor α-1, collagen Type 1 alpha-1, or nuclear factor of activated T cells c1. In conclusion, increased trabecular bone with additional zinc suggests that previous requirement estimates of 15 μg Zn/g diet may not meet nutritional needs for optimal bone development. Overall, the up-regulation of extracellular matrix modeling indexes and concomitant decrease in resorption activities as dietary zinc increased from 2.5 to 30 μg/g provide evidence of one or more physiological roles for zinc in modulating the balance between bone formation and resorption.     

The development of bone changes induced in rats by recombinant human granulocyte colony-stimulating factor is suppressed by bisphosphonate.

We have previously demonstrated that high doses of recombinant human granulocyte colony-stimulating factor (rhG-CSF) induce bone changes characterized by osteoclastic bone resorption and osteogenesis due to intramembranous ossification in rats. In this communication we examined the effects of a pretreatment with 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP), which is a powerful inhibitor of osteoclastic bone resorption, on bone changes induced by rhG-CSF in order to investigate the relation between osteoclastic bone resorption and osteogenesis. AHPrBP (5 mg/kg/day) was subcutaneously given to 6-week-old rats for 2 days. From the following day of the final injection of AHPrBP, rats received a subcutaneous injection of rhG-CSF (1,000 micrograms/kg/day) for 14 days, and the femur and tibia were evaluated histopathologically. By the analysis of peripheral blood leukocyte counts, spleen weights and bone marrow findings, the pretreatment with AHPrBP had no effect on the activation of hematopoiesis related to the major pharmacological activity of rhG-CSF. In the rats treated with rhG-CSF alone, accelerated osteoclastic bone resorption and osteogenesis due to intramembranous ossification were observed in the trabeculae of metaphyseal spongiosa. The accelerated osteoclastic bone resorption induced by rhG-CSF was suppressed by the pharmacological activity of AHPrBP. Furthermore, the osteogenesis induced by rhG-CSF was also suppressed by AHPrBP. These results suggest that the osteogenesis induced by rhG-CSF is a sequential reaction of accelerated osteoclastic bone resorption, and moreover that the main action of rhG-CSF on bone is an acceleration of osteoclastic bone resorption.     

RANKL from bone marrow adipose lineage cells promotes osteoclast formation and bone loss

Receptor activator of NF‐κB ligand (RANKL) is essential for osteoclast formation and bone remodeling. Nevertheless, the cellular source of RANKL for osteoclastogenesis has not been fully uncovered. Different from peripheral adipose tissue, bone marrow (BM) adipose lineage cells originate from bone marrow mesenchymal stromal cells (BMSCs). Here, we demonstrate that adiponectin promoter‐driven Cre expression (Adipoq^Cre ) can target bone marrow adipose lineage cells. We cross the Adipoq^Cre mice with rankl^fl/fl mice to conditionally delete RANKL from BM adipose lineage cells. Conditional deletion of RANKL increases cancellous bone mass of long bones in mice by reducing the formation of trabecular osteoclasts and inhibiting bone resorption but does not affect cortical bone thickness or resorption of calcified cartilage. Adipoq^Cre; rankl^fl/fl mice exhibit resistance to estrogen deficiency and rosiglitazone (ROS)‐induced trabecular bone loss but show bone loss induced by unloading. BM adipose lineage cells therefore represent an essential source of RANKL for the formation of trabecula osteoclasts and resorption of cancellous bone during remodeling under physiological and pathological conditions. Targeting bone marrow adiposity is a promising way of preventing pathological bone loss.     

Influence of dietary NaCl on L-arginine transport in the renal medulla

Previous work demonstrated that l-arginine, the substrate for nitric oxide (NO) synthase, is carried into inner medullary collecting duct (IMCD) cells via system y+, that the major system y+ gene product in IMCD is the cationic amino acid transporter 1 (CAT1), and that blockade of l-arginine uptake in the renal medulla decreases NO and leads to systemic hypertension. The present study determined the influence of dietary sodium intake on l-arginine uptake in IMCD, on CAT1 immunoreactive protein in the renal medulla, and on the hypertensive response to blockade of l-arginine uptake in the renal medulla. Transport studies in bulk-isolated IMCD demonstrated that l-arginine uptake by IMCD was significantly greater (663 +/- 100 pmol x mg(-1) x min(-1), n = 6) in rats exposed to a low-sodium diet (0.4% NaCl) compared with rats on a normal (1% NaCl, 519 +/- 78 pmol x mg(-1) x min(-1), n = 6) or high-sodium diet (4.0% NaCl, 302 +/- 27 pmol x mg(-1) x min(-1), n = 6). Immunoblotting experiments demonstrated that CAT1 immunoreactive protein was significantly decreased by approximately 30% in rats maintained on a high-NaCl diet (n = 5) compared with rats on a low-NaCl diet (n = 5). In contrast to the l-arginine transport and immunoblotting data, in vivo blockade of l-arginine uptake led to hypertension of equal magnitude in rats maintained on a low- or high-NaCl diet. These results indicate that sodium loading leads to a decrease in immunoreactive CAT1 protein in the rat renal medulla, resulting in decreased l-arginine uptake capacity. The decrease in l-arginine uptake capacity, however, does not alter the blood pressure response to l-arginine uptake inhibition in the renal medulla.     

Aluminium-induced bone disease in uremic Rats: Effect of deferoxamine

We have previously established a rat model of chronic uremia, which is suitable to investigate the effect of various treatment modalities on renal osteodystrophy [1]. After four months subsequent to 5/6 nephrectomy, some animals were treated by gavage for 9 weeks with tap water (controls), or with aluminium (Al-citrate) 3 × 25 mg/week/kg b.wt ± subsequent deferoxamine (DFO) 3 × 50 mg/ week/kg b.wt. for 4 weeks. At termination of the study, serum clinical chemistry, femoral chemical composition and mechanical properties, calvarial parathyroid hormone (PTH)-elicited adenylate cyclase (AC) and phospholipase C (PLC) activities, cross-sectional femoral area, as well as bone histomorphometry, were analyzed. Animals given Al displayed moderately enhanced serum Al and bone Al accumulation, however, DFO-treatment did not fully alleviate bone Al retainment. A small increase in serum PTH was seen in all animals rendered uremic. Furthermore, a marked fall in serum alkaline phosphatase (ALP) below normal controls was observed in Al ± DFO-treated animals compared with uremic controls. The uremic condition led to reduced femoral ratios of hydroxyproline (HYP) over Ca²⁺ and phosphate (P_i), while Al-intoxication alone enhanced femoral Hyp contents above values seen for normal controls. The protracted ureamia caused a deterioration of long bone resilience and brittleness, however, Al ± DFO-treatment seemed to normalize the latter. Contrastingly, Al ± DFO-gavage enhanced time to fracture. Uremic rats intoxicated with Al showed a complete loss of calvarial PTH-sensitive AC and PLC activities. DFO-treatment normalized PTH-elicited PLC, while PTH-susceptible AC remained super-normal. Al apparently exerts a long term down-regulation of both PTH-sensitive signaling systems as evidenced by studies of rat UMR 106 osteosarcoma cells in culture. The uremic condition enhanced endosteal bone resorption as shown by femoral shaft dimension analysis, while AI ± DFO-treatment insignificantly reversed the condition. Finally, histomorphometrical analyses showed that DFO-administration tended to normalize aberrant trabecular bone volume, while rectifying both bone resorption and degree of mineralization. In conclusion, we assert that Al-intoxication hampers both processes (i.e. formation and resorption) of bone turnover, and that DFO-treatment to a certain extent prevents the uremia- and Al-induced bone disease in rats.     

Dietary sodium modulates the interaction between efferent and afferent renal nerve activity by altering activation of α2-adrenoceptors on renal sensory nerves

Activation of efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which then reflexively decreases ERSNA via activation of the renorenal reflexes to maintain low ERSNA. The ERSNA-ARNA interaction is mediated by norepinephrine (NE) that increases and decreases ARNA by activation of renal α(1)-and α(2)-adrenoceptors (AR), respectively. The ERSNA-induced increases in ARNA are suppressed during a low-sodium (2,470 ± 770% s) and enhanced during a high-sodium diet (5,670 ± 1,260% s). We examined the role of α(2)-AR in modulating the responsiveness of renal sensory nerves during low- and high-sodium diets. Immunohistochemical analysis suggested the presence of α(2A)-AR and α(2C)-AR subtypes on renal sensory nerves. During the low-sodium diet, renal pelvic administration of the α(2)-AR antagonist rauwolscine or the AT1 receptor antagonist losartan alone failed to alter the ARNA responses to reflex increases in ERSNA. Likewise, renal pelvic release of substance P produced by 250 pM NE (from 8.0 ± 1.3 to 8.5 ± 1.6 pg/min) was not affected by rauwolscine or losartan alone. However, rauwolscine+losartan enhanced the ARNA responses to reflex increases in ERSNA (4,680 ± 1,240%·s), and renal pelvic release of substance P by 250 pM NE, from 8.3 ± 0.6 to 14.2 ± 0.8 pg/min. During a high-sodium diet, rauwolscine had no effect on the ARNA response to reflex increases in ERSNA or renal pelvic release of substance P produced by NE. Losartan was not examined because of low endogenous ANG II levels in renal pelvic tissue during a high-sodium diet. Increased activation of α(2)-AR contributes to the reduced interaction between ERSNA and ARNA during low-sodium intake, whereas no/minimal activation of α(2)-AR contributes to the enhanced ERSNA-ARNA interaction under conditions of high sodium intake.     

A novel method to 'exercise' rats: making rats rise to erect bipedal stance for feeding - raised cage model

We employed a novel method to exercise rats: making them rise to bipedal stance for feeding using raised cages. We studied its effects on the skeletons of 6 and 10-month-old intact or orchidectomized (ORX) rats. Body and hindlimb muscle weights, tibial BMC and periosteal cortical bone formation increased after housing in raised cages, but more so in 6-month-old animals than in 10-month-old ones. In 6-month-old orchidectomized rats, raised cages partially prevented ORX-induced bone loss by stimulating periosteal cortical bone (TX) formation and decreased bone resorption next to marrow. In 10-month-old male orchidectomized rats, raised cages also decreased the endosteal and trabecular bone resorption, but not enough to prevent completely ORX-induced net bone losses. Because the osteogenic effects of raised cages alone were only partial, we also studied the interaction between raised cage and prostaglandin E(2) (PGE(2)) in 10-month-old retired female breeders. When treated with combined raised cage and PGE(2), both cortical (TX) and trabecular bone mass of the proximal tibial metaphysis and lumbar vertebral body increased over either raised cages or PGE(2) treatment alone, that was accompanied by dramatic increased bone formation at periosteal and endosteal surfaces. Thus making rats rise to erect bipedal stance for feeding helps to prevent bone loss after orchidectomy; it amplifies the anabolic effects of PGE(2), and it provides an inexpensive, non-invasive and reliable way to increase mechanical loading of certain bones of the rat skeleton.     

Constitutively Elevated Blood Serotonin Is Associated with Bone Loss and Type 2 Diabetes in Rats

Reduced peripheral serotonin (5HT) in mice lacking tryptophan hydroxylase (TPH1), the rate limiting enzyme for 5HT synthesis, was reported to be anabolic to the skeleton. However, in other studies TPH1 deletion either had no bone effect or an age dependent inhibition of osteoclastic bone resorption. The role of 5HT in bone therefore remains poorly understood. To address this issue, we used selective breeding to create rat sublines with constitutively high (high-5HT) and low (low-5HT) platelet 5HT level (PSL) and platelet 5HT uptake (PSU). High-5HT rats had decreased bone volume due to increased bone turnover characterized by increased bone formation and mineral apposition rate, increased osteoclast number and serum C-telopeptide level. Daily oral administration of the TPH1 inhibitor (LX1032) for 6 weeks reduced PSL and increased the trabecular bone volume and trabecular number of the spine and femur in high-5HT rats. High-5HT animals also developed a type 2 diabetes (T2D) phenotype with increased: plasma insulin, glucose, hemoglobin A1c, body weight, visceral fat, β-cell pancreatic islets size, serum cholesterol, and decreased muscle strength. Serum calcium accretion mediated by parathyroid hormone slightly increased, whereas treatment with 1,25(OH)₂D₃ decreased PSL. Insulin reduction was paralleled by a drop in PSL in high-5HT rats. In vitro, insulin and 5HT synergistically up-regulated osteoblast differentiation isolated from high-5HT rats, whereas TPH1 inhibition decreased the number of bone marrow-derived osteoclasts. These results suggest that constitutively elevated PSL is associated with bone loss and T2D via a homeostatic interplay between the peripheral 5HT, bone and insulin.     

High sodium chloride intake exacerbates immobilization-induced bone resorption and protein losses

We examined, in immobilization, the effect of a diet high in sodium chloride (NaCl) on bone markers, nitrogen balance, and acid-base status. Eight healthy male test subjects participated in a 14-day head-down-tilt bed rest (HDBR) study. During the bed rest period they received, in a randomized crossover design, a high (7.7 meq Na(+)/kg body wt per day) and a low (0.7 meq Na(+)/kg body wt per day) NaCl diet. As expected, 24-h excretion of urinary calcium was significantly greater in the high-NaCl-intake HDBR phase than in the low-NaCl-intake HDBR phase (P < 0.001). High NaCl intake caused a 43-50% greater excretion of the bone resorption markers COOH- (CTX) and NH(2)- (NTX) terminal telopeptide of type I collagen in HDBR than low NaCl in HDBR (CTX/NTX: P < 0.001). Serum concentrations of the bone formation markers bone-specific alkaline phosphatase (bAP) and NH(2)-terminal propeptide of type I procollagen (PINP) were identical in both NaCl intake phases. High NaCl intake led to a more negative nitrogen balance in HDBR (P < 0.001). Changes were accompanied by increased serum chloride concentration (P = 0.008), reduced blood bicarbonate (P = 0.017), and base excess (P = 0.009) whereas net acid excretion was lower during high than during low NaCl intake in immobilization (P < 0.001). High NaCl intake during immobilization exacerbates disuse-induced bone and muscle loss by causing further protein wasting and an increase in bone resorption. Changes in the acid-base status, mainly caused by disturbances in electrolyte metabolism, seem to determine NaCl-induced degradation processes.     

The effect of conjugated linoleic acid on calcium absorption and bone metabolism and composition in adult ovariectomised rats

The effect of conjugated linoleic acid (CLA) on postmenopausal bone metabolism has not been investigated. Therefore, forty-three adult ovariectomised (OVX) rats (8-9 rats per group) were fed either a control diet containing 40 g/kg soyabean oil (SBO diet) or the SBO diet with 0 (control OVX), 2.5, 5 or 10 g/kg of CLA (replacing soybean oil) for 9 weeks. A group of sham-operated (SH) rats were fed the SBO diet. OVX rats had significantly (P<0.05) lower femoral bone mineral density and macromineral concentration, and intestinal Ca absorption compared to SH rats. CLA supplementation had no effect on these parameters. Ex vivo PGE(2) biosynthesis by bone and urinary Pyr and Dpyr (markers of bone resorption) were significantly higher (P<0.001) in control OVX rats compared with SH rats, and were significantly (P<0.001) lowered by CLA supplementation with 5 and 10, but not 2.5 g/kg diet in OVX rats. In conclusion, CLA supplementation appeared to reduce the rate of bone resorption in adult OVX rats.     

A calcitonin-like action of prostaglandin E1

The pharmacological effects of PGE₁ (6 and 9 days, 21,250 μg/kg per day subcutaneously) upon the growth and the bone resorption of mammals were studied using the proximal tibia and upper incisor of immature rats along with lead acetate as a time marker, and upon the serum calcium and inorganic phosphorus levels. The following results were obtained. 1. PGE₁ hardly affected the body weight or the weight of organs of the rats but apparently inhibited the longitudinal growth of proximal tibia in a dose related manner. 2. PGE₁ clearly inhibited not only the longitudinal growth (incisor growth) but also the appositional growth (dentin formation) of incisal dentin. 3. The grade of the inhibitory effect on the growth was in the order of bone growth >dentin formation >incisor growth. 4. The occurrence of osteoporosis due to a low calcium diet was inhibited by the simultaneous administration of PGE₁, the mechanism being considered to be mainly due to the inhibitory effect on the bone resorption. 5. PGE₁ lowered the level of serum calcium and the lowering effect was not observed in the thyro-parathyroidectomized rat. From the facts that the above effects were exactly the same as those of calcitonin (1), the possibility that the subcutaneous injection of PGE₁ may induce a calcitonin-like action, a part of which may dependent on the calcinonin secretion is suggested.     

Preventive effects of risedronate and calcitriol on cancellous osteopenia in rats treated with high-dose glucocorticoid.

We compared the effects of risedronate (Ris) and calcitriol (Cal) on cancellous osteopenia in rats treated with high-dose glucocorticoid (GC). Forty female Sprague-Dawley rats, 4 months of age, were randomized by the stratified weight method into four groups of 10 rats each according to the following treatment schedule: intact control, and GC administration with vehicle, Ris, or Cal. The GC (methylprednisolone sodium succinate, 5.0 mg/kg, s.c.), Ris (10 microg/kg, s.c.), and Cal (0.1 microg/kg, p.o.) were administered 3 times a week. At the end of the 4-week treatment period, bone histomorphometric analysis was performed for cancellous bone of the proximal tibial metaphysis. The GC administration decreased cancellous bone volume (BV/total tissue volume [TV]), trabecular number (Tb N), and trabecular thickness (Tb Th), as a result of increased bone resorption and decreased bone formation. Ris treatment markedly increased cancellous BV/TV and Tb N above the control level as a result of suppressed bone turnover. On the other hand, Cal treatment attenuated the GC-induced decrease in cancellous BV/TV and Tb Th as a result of suppressed bone resorption and maintained bone formation. This study showed the differential effects of Ris and Cal on cancellous osteopenia in rats treated with high-dose GC.     

The effect of resorption cavities on bone stiffness is site dependent

Resorption cavities formed during the bone remodelling cycle change the structure and thus the mechanical properties of trabecular bone. We tested the hypotheses that bone stiffness loss due to resorption cavities depends on anatomical location, and that for identical eroded bone volumes, cavities would cause more stiffness loss than homogeneous erosion. For this purpose, we used beam–shell finite element models. This new approach was validated against voxel-based FE models. We found an excellent agreement for the elastic stiffness behaviour of individual trabeculae in axial compression (R² = 1.00) and in bending (R²>0.98), as well as for entire trabecular bone samples to which resorption cavities were digitally added (R² = 0.96, RMSE = 5.2%). After validation, this new method was used to model discrete cavities, with dimensions taken from a statistical distribution, on a dataset of 120 trabecular bone samples from three anatomical sites (4th lumbar vertebra, femoral head, iliac crest). Resorption cavities led to significant reductions in bone stiffness. The largest stiffness loss was found for samples from the 4th lumbar vertebra, the lowest for femoral head samples. For all anatomical sites, resorption cavities caused significantly more stiffness loss than homogeneous erosion did. This novel technique can be used further to evaluate the impact of resorption cavities, which are known to change in several metabolic bone diseases and due to treatment, on bone competence.