Trabecular and endocortical bone remodeling in postmenopausal osteoporosis: Comparison with normal postmenopausal women

To assess the bone turnover abnormalities which characterize postmenopausal osteoporosis with vertebral fractures (PMOp), a transiliac bone biopsy was performed after double labeling of the mineralizing front with tetracycline in 50 untreated PMOp patients who were compared with 13 healthy age-matched volunteer females. The analysis of bone remodeling and structure parameters demonstrated that PMOp is a disease affecting both the cancellous and the endocortical envelopes and characterized by increased resorption and by a marked decrease in the osteoblastic apposition rate due to a reduced duration of bone formation. This induces a decrease in the width of both individual osteons and trabeculae. In PMOp, the wide spectrum of bone turnover as compared with the controls, associated with the typical bimodal distribution of cancellous osteoid perimeter, allowed us to identify two subsets, one with normal turnover (NT) and one with high turnover (HT) representing 30% of the cases. When compared to NT, HT was characterized by increased osteoclast number, lower bone volume, thinner osteons, increased formation at the tissue-level and markedly decreased duration of formation. In HT the marked decrease in the duration of activity of osteoblasts and the markedly increased number of osteoclasts induced a greater decrease in bone volume, despite the increase of bone formation at the tissue level. These subsets could not be distinguished by any clinical or biochemical parameter except for serum bone gla protein (osteocalcin) which was significantly higher (as a group) in HT than in NT. The underlying cause for these two subsets is unknown. We conclude that PMOp affects the cancellous and the endocortical bone. Bone loss results from a wide spectrum of bone turnover abnormalities, with two distinct subsets, one with normal turnover and one with high turnover.     

谷康泰灵对骨质疏松模型大鼠骨形成和骨吸收功能的影响

目的　观察药物谷康泰灵对骨质疏松 (OP)模型大鼠骨形成和骨吸收功能的影响 ,为其临床治疗骨质疏松提供实验依据。方法　SD大鼠 4 4只 ,随机分为正常组 (13只 )和骨质疏松模型组 (31只 )。以维甲酸 80mg·kg- 1 ·d- 1 灌胃 15d,诱导OP模型。模型复制成功后 ,各组处死 5只 ,正常组 (8只 )继续观察 ,模型组又随机分为无措施对照组 (8只 )、谷康泰灵治疗组 (10只 ,0 0 8mg·kg- 1 ·d- 1 谷康泰灵腹腔注射 )和雌二醇治疗组 (8只 ,每只 0 0 5mg,每周 3次苯甲酸雌二醇腹腔注射 )。治疗期 30d。观察股骨松质骨区成骨细胞及破骨细胞数量和血清中AKP、TRAP活性变化。结果　与正常组相比 ,维甲酸诱导的OP模型大鼠股骨松质骨区成骨细胞功能活跃 ,数量变化不大 ;破骨细胞数量、活跃程度显著增加 ;血清中AKP和TRAP明显增高。谷康泰灵治疗后 ,OP大鼠活跃成骨细胞数量明显增加 ,破骨细胞数量显著减少 ,血清AKP活性明显增高 ,TRAP活性下降。结论　谷康泰灵对OP大鼠骨形成和骨吸收功能有显著影响 ,可刺激成骨细胞的产生增加成骨细胞的活性 ,减少破骨细胞的数量抑制破骨细胞的活性。     

Effect of testosterone therapy on bone formation in an osteoporotic hypogonadal male

Summary Osteoporosis has been reported to complicate androgen deficiency in males. Accordingly, we have evaluated an osteoporotic hypogonadal male with bone histomorphometry before and after 6 months of testosterone replacement. Androgen therapy resulted in increases in relative osteoid volum, total osteoid surface, linear extent of bone formation, and bone mineralization. The dramatic histological response to hormonal replacement confirms the importance of androgens in bone modeling and remodeling.     

Reduced bone formation in patients with osteoporosis associated with inflammatory bowel disease

The pathophysiology of bone loss associated with inflammatory bowel disease has not been clearly defined. In this study we have performed a detailed histomorphometric analysis of iliac crest bone obtained from 19 patients with inflammatory bowel disease in whom a diagnosis of osteoporosis had been made. Eleven subjects were receiving prednisolone at the time of their biopsy. Comparison with control values demonstrated a highly significant reduction in trabecular bone area in the patient group (p<0.001). Wall width, adjusted appositional rate and bone formation rate were all significantly reduced in the patient group (p<0.001) and the formation period was significantly increased (p<0.001). Resorption cavities were slightly smaller in the patient group, differences in maximum cavity depth and cavity length achieving statistical significance (p<0.005 andp<0.05 respectively). The mineral appositional rate was significantly reduced in the patients with inflammatory bowel disease (p<0.001) and the mineralization lag time significantly increased (p<0.001); however, osteoid area, perimeter and seam width were not significantly different from controls. These results demonstrate that osteoporosis associated with inflammatory bowel disease is characterized by reduced bone formation at the cellular and tissue level; the proportionately greater change in wall width than in resorption cavity depth is consistent with a negative remodelling balance. Although none of the patients had osteomalacia as defined by the criteria of increased osteoid seam width and mineralization lag time, the higher mineralization lag time in the patient group indicates a mild mineralization defect.     

Can serum osteocalcin levels predict bone turnover in patients with osteoporosis?

The assessment of bone metabolism by biochemical markers remains difficult problem. Serum osteocalcin, synthesized in bone cells, is now becoming a sensitive indicator of bone turnover in patients with metabolic bone diseases. We measured serum osteocalcin levels by radioimmunoassay in 18 patients with osteoporosis and examined whether they reflect bone formation, resorption or both. We found that serum osteocalcin levels in biopsy-identified osteoporotics were widely ranged (1.8 – 18.8 ng/ml). Tetracycline double labeling method exibited two types of labeling pattern in the iliac bone, that is double labeled or no double labeled (impaired labeled) pattern. Serum concentrations of osteocalcin in patients with double labeling were significantly higher than those with impaired labeling (11.2±4.0 vs 4.1 ±2.1 ng/ml, P<0.01). Furthermore, serum osteocalcin levels showed a significantly positive linear correlation with the parameters reflecting bone formation, but not with bone resorption. These data indicate that serum osteocalcin levels reflect bone formation in osteoporotics and thereby could be a useful indicator of osteoblastic function in osteoporosis.     

Mean wall thickness and formation periods of trabecular bone packets in corticosteroid-induced osteoporosis

Summary We have compared the mean wall thickness (MWT) and active formation periods (sigma_f(A)) of trabecular bone packets in iliac crest biopsies from 20 patients (7 male, 13 female) with corticosteroid-induced osteoporosis (CS-OP) and 20 age- and sex-matched controls. The trabecular bone volume (TBV) of the CS-OP patients (9.6%±2.2% [SD]) was significantly reduced compared to controls (19.3%±5.1%). The MWT of CS-OP patients (32.7±4.3 μm) was also significantly lower than the control value (48.0±6.2 μm). There was a positive correlation between MWT and TBV in both groups. The mineralization rate (M) of the CS-OP patients (0.54±0.25 μm/day) was within the normal range, and since there was no increase in osteoid seam thickness, so therefore was the osteoblastic appositional rate (OAR). The active formation period of trabecular bone packets (sigma_f(A)=MWT/M) was significantly lower in the CS-OP patients (55.9 ± 14.4 days) than in the control group (68.1 ± 9.4 days). MWT and sigma_f(A) both decreased with age in the control group, whereas in the CS-OP group they were independent of age. We conclude that corticosteroid therapy results in a reduction of the MWT of trabecular bone packets and, consequently, of TBV. In these patients, where the OAR was normal, the reduction in MWT was apparently caused by a shortening of the lifespan of the active osteoblastic population at the basic multicellular unit (BMU) level. This work is dedicated to the late Professor Rudolfo Amprino in appreciation of his great contribution to the field of bone research.     

Mean wall thickness and formation periods of trabecular bone packets in idiopathic osteoporosis

Summary The mean wall thickness (MWT) and duration of formation periods (sigma_f) of trabecular bone packets have been measured in iliac crest biopsies following double tetracycline labeling from 9 women having primary osteoporosis, with vertebral crush fractures and reduced trabecular bone volume (TBV), and 9 age- and sex-matched controls. The MWT of the osteoporotic biopsies was significantly less than that of the controls and was negatively correlated with age in the latter. There was also a positive correlation between MWT and TBV in the controls but not in the osteoporotics. Sigma_f, in days, showed a tendency to decline with age in the control biopsies and was further decreased in the osteoporotic patients. These results suggest that a major contribution to the negative skeletal balance existing in both primary osteoporosis and physiological osteopenia is a decrease in bone formation, caused by a reduction in the life span of the osteoblastic population at the basic multicellular unit (BMU) level.     

Absence of mouse pleiotrophin does not affect bone formation in vivo

Pleiotrophin (Ptn) is an extracellular matrix protein that regulates hippocampal synaptic plasticity and learning behavior in vivo. Since the overexpression of Ptn in transgenic mice leads to increased bone formation, we analyzed whether a deficiency in Ptn expression would have a negative effect on bone remodeling. Bones from Ptn-deficient mice and wild-type littermates were analyzed using radiography, μCT imaging and undecalcified histology. Biomechanical stability was determined in a three-point-bending assay. Cellular activities were assessed using dynamic histomorphometry and the determination of urinary collagen degradation products. Skeletons of Ptn-deficient mice have no gross abnormalities, displayed a normal size, and showed no differences in growth plate organization compared to wild-type littermates. There were no obvious differences in bone mass as determined by radiographic and μCT imaging. The absence of a bone remodeling phenotype in Ptn-deficient mice was further confirmed using static histomorphometry and biomechanical testing. Finally, the number, morphology, and function of osteoclasts, osteoblasts, and osteocytes were not altered in Ptn-deficient mice compared to wild-type littermates. The complete skeletal analysis of Ptn-deficient mice presented here demonstrates that the lack of Ptn in mice does not affect bone formation in vivo. Therefore, Ptn does not play a significant role in normal bone physiology.     

Histomorphometric analysis of iliac crest bone biopsies in placebo-treated versus fluoride-treated subjects

In a 4-year controlled, prospective trial, histomorphometric analysis was used to compare the tissue-level skeletal effects of fluoride therapy in 43 postmenopausal women (75 mg NaF/day) with those of 35 matching placebo subjects; all subjects received 1500 mg/day elemental calcium supplement. In addition to an initial, baseline biopsy, a second biopsy was obtained after 6, 18, 30 or 48 months. Measurements were made on a third biopsy obtained from 8 subjects following at least 72 months of fluoride therapy. The change in cancellous bone volume or trabecular thickness in fluoride-treated subjects was not different from a change in placebo-treated subjects. However, paired analysis in the fluoride-treated subjects indicated that bone volume was increased between the first and second biopsies (p<0.005). Both osteoid length and width were significantly increased in fluoride compared with placebo subjects; however, only the osteoid surface increased linearly (r=0.63,p<0.001). The mineral apposition rate and relative tetracycline-covered bone surface were not different between fluoride and placebo treatment, although they were decreased in both groups in the second biopsy. The tetracycline-covered bone surface returned to normal in the third biopsy. Definitive evidence for osteomalacia is a prolonged mineralization lag time, which following fluoride treatment was found to be increased 9-fold in the second biopsy and 4-fold in the third biopsy. Further evidence for osteomalacia was increased osteoid thickness by 6 months, evidence of focal areas of interstitial mineralization defects, and broad tetracycline labels of low fluorescence intensity. In the third biopsies, osteoclastic resorption was observed beneath osteoid seams. Fluoride therapy increased the cortical width compared with placebo treatment (p<0.02), and increased the osteoid surface in Haversian canals, but did not change the osteoid width, resorption surface or cortical porosity. After an initial rise, serum fluoride levels remained constant, and the urine values fell slightly. The bone fluoride concentration rose throughout the treatment period, and was correlated with the change in osteoid-covered bone surface (r=0.56,p<0.001). Although we found definitive evidence for osteomalacia, the cause of the osteomalacia was not determined in this study. On the other hand, the presence of bone resorption beneath unmineralized osteoid and of osteocyte halos is suggestive of hyperparathyroidism. Thus, it is possible that the strong stimulus for bone formation brought about by fluoride therapy resulted in relative calcium deficiency.     

Implant-induced microdamage in osteoporotic bone

With the increase of elderly population,more and more implant operations need to be performed in osteoporotic bone,while different forms of microdamage will be produced in peri-implant bone intraoperat...     

Glucocorticoid-induced inhibition of osteoblastic bone formation in ewes: A biochemical and histomorphometric study

The mechanisms underlying glucocorticoid-induced osteoporosis in humans are a defect in bone formation associated with increased bone resorption. The latter may be due to elevated parathyroid hormone (PTH) levels induced by the impairment of intestinal calcium absorption caused by corticosteroids. In this study we analysed the effects of corticosteroids in old ewes, a potential model for the study of human bone turnover. Two groups of seven 9-year-old female sheep were selected. The first group was injected intramuscularly with a daily dose of 30 mg methylprednisone (MP) during the first 2 months and 15 mg during the last month. After 2 and 3 months of treatment, blood samples were taken. At the end of the experiment the animals were slaughtered and the iliac crest kept for bone histomorphometry. Serum osteocalcin (sOC) rapidly and markedly decreased in the MP-treated group compared with controls (–77%;p<0.01). In contrast, at the end of the experiment serum calcium and PTH levels were similar in both groups. Histomorphometric analysis showed a significant reduction in the wall width of trabecular packets. Dynamic parameters reflecting bone formation at the tissue and cell levels were significantly lower in the MP-treated group than in controls, with a highly significant decrease in the mineralization rate (MAR: –63%,p<0.05) and double-labeled perimeter (dLPm/B.Pm: –92%p<0.05). The bone formation rate (BFR/B.Pm) also decreased by 84% and the adjusted apposition rate (Aj.AR) by 80%. The increase in the total formation period was mainly due to an increase in the inactive period. Significant correlations were found between sOC and MAR, dLPm/B.Pm and BFR/B.Pm (withr respectively 0.67, 0.76 and 0.51). In conclusion, the effects of corticosteroid on ewe bone remodeling are essentially characterized by a major bone formation defect without evidence of secondary hyperparathyroidism, although this cannot be totally excluded by our results. Ewes treated with glucocorticoids could represent a good model for evaluating the effects of drugs candidates for all bone conditions characterized by reduced bone formation resulting from osteoblastic depression.     

Fewer bone histomorphometric abnormalities with intermittent than with continuous slow-release sodium fluoride therapy

To help resolve the uncertainty whether sodium fluoride (NaF) therapy should be given intermittently or continuously, we examined iliac crest bone biopsies (before and after treatment) and fragility fracture rates in 35 intermittently treated (group I) and 69 continuously treated (group C) patients; all received calcium. The following statistically significant results were obtained. Reduction in vertebral fracture rate was similar in the two groups. Trabecular thickness and the structurally more important mineralized thickness increased only in group I. Group I also accumulated less excess osteoid (surface, volume). Mean osteoid thickness did not change in either group because of a bimodal distribution of wide seams with osteoblasts and double tetracycline labels, and thin seams without osteoblasts or labels. Osteoid was lamellar. Osteoid in abnormal sites (within bone marrow or bone, or around osteocytes) was found less frequently in group I. Adjusted apposition rate declined and mineralization lag time increased in both groups because of extended unlabelled osteoid seams. Erosion surface increased only in group C. Hook and/or tunnel erosion was seen less frequently in group I; it was closely associated with osteoid in abnormal sites and correlated with osteoid surface. Extended osteoid surface may have forced osteoclasts to hollow out trabeculae, leaving the empty osteoid shell in marrow. Excess osteoid volume and eroded surface and osteoid and erosion in abnormal sites correlated with bone fragility in group C. We conclude that intermittent therapy is to be preferred because it (1) increased mineralized trabecular thickness, (2) did not cause excessive osteoid accumulation and erosion, (3) showed less osteoid and erosion in abnormal sites and (4) led to a similar reduction in the vertebral fracture rate as did continuous treatment. The question of whether intermittency of therapy has some other effect independent of the cumulative dose of fluoride administered cannot be answered by this study.     

Biophysical study of bone mineral in biopsies of osteoporotic patients before and after long-term treatment with fluoride

Crystallographic characteristics of bone mineral were examined in a group of 60 osteoporotic patients before and after 3 to 6 years of fluoride therapy. The age of the mineral was evaluated by means of X-ray absorption, as degree of mineralization of bone tissue (MDBT). Crystallinity was evaluated by measuring both X-ray diffraction line broadening, β (31.0) and β (00.2), and the crystallinity index (CI) by infrared spectrometry. The a and c unit-cell parameters were determined by powder X-ray diffraction. Bone fluoride content was measured by specific electrode.

Patients were divided in two groups according to MDBT before treatment: one group with MDBT values less than or equal to mean value; another group with MDBT values greater than mean value. In the first group, trabecular bone volume (TBV) did not change significantly during therapy. In the second group, an increase of TBV was observed. Osteoporoses can then be distinguished, on MDBT criterion, between osteoporosis with hypermaturated mineral and osteoporosis with hypomaturated mineral. The MDBT before treatment permits one to predict the effect of fluoride therapy on TBV.

In the two groups there was a significant increase in bone fluoride content between the onset and the end of treatment. Bone fluoride content increased linearly during therapy without any plateau effect. Crystallographic modifications induced by fluoride explain the mechanical and chemical improvement of bone.     

辛伐他汀体外促进骨形成作用的初步研究

目的 研究辛伐他汀(Simvastatin)对成骨细胞分化、增殖及骨形成的作用。方法 用RPMI 1640培养液分别对水囊引产胎儿及新生大鼠颅顶骨进行组织培养,并将等量的胎儿或大鼠的颅顶骨骨组织分为实验组(辛伐他汀1μmol/L)和对照组,除动态观察比较不同培养液中成骨细胞的增殖状况外,将培养7d后的颅顶骨组织块制成半薄或超薄病理切片,于光镜下和电镜下进行形态学观察,并用测微尺测量新生骨组织厚度,记录成骨细胞数;同时,对留取的培养液测定其中的碱性磷酸酶(AKP)及骨钙素(BGP)的含量。结果 在培养过程中,可见实验组胎儿和新生大鼠颅骨成骨细胞生长活跃,数量多;对照组成骨细胞生长缓慢,数量少,可见大量成纤维细胞。培养7d后可见实验组胎儿及大鼠颅骨新生骨组织的厚度均明显高于对照组(P<0.01);其单位长度(0.3 mm)新生骨组织内成骨细胞数均明显高于对照组(P<0.01)。透射电镜下可见实验组成骨细胞处于活化状态,胞浆内有丰富的细胞器,少见破骨细胞,而对照组成骨细胞处于衰老状态,细胞器少见,可见大量破骨细胞。实验组培养液中AKP及BGP均明显高于对照组(P<0.01)。结论 辛伐他汀在体外实验中具有促进成骨细胞分化、增殖和促进新骨形成的作用;他汀类药物可作为预防、治疗骨质疏松症的有价值的候选药物。     

Bone particles disturb new bone formation on the interface of the titanium implant after reaming of the marrow cavity

Histomorphometric studies were conducted in rats to determine whether bone particles would disturb new bone formation on the interface of titanium implants inserted after reaming of the marrow cavity. In eighty 10-week-old female Wistar rats, smooth-surfaced titanium alloy implants were inserted bilaterally into the marrow cavity after reaming in the distal femur. There were three experimental groups: in the irrigated femora, sterile saline was flushed through the medullary canal; in the particle femora, autologous bone particles were inserted into the intramedullary cavity; and in the reamed femora, the implant was inserted without procedures after reaming. The rats were sacrificed at one, two, four or eight weeks postoperatively, and Villanueva bone staining was applied for histomorphometric studies. The bone volume of new bone on the interface of the implant in the irrigated femora was greater than that in the particle or the reamed femora throughout the study period. The results suggest that clearance of bone particles by irrigation after reaming of the marrow cavity significantly facilitates new bone formation on the interface of implants by one week. The findings also suggest the potential clinical application of total canal irrigation prior to insertion of cementless femoral components as well as cemented prosthesis.     

骨源性碱性磷酸酶预测骨质疏松骨折患者再骨折的意义

目的探讨骨质疏松患者初次骨折后发生再骨折的影响因素,分析血清骨源性碱性磷酸酶(BALP)对预测再发骨折的临床价值。方法前瞻性队列研究纳入我院178例确诊的50岁以上骨质疏松性骨折患者。初次骨折时检测患者血清BALP水平、骨密度值(BMD)、钙、磷及临床一般资料等,跟踪随访4年,以患者再发骨折为随访终点事件。采用Kaplan-Meier分析和多元Cox回归模型进行再发骨折的风险因素研究,受试者工作特征(ROC)曲线用于评判BALP的预测价值。结果 178例骨质疏松性骨折患者4年内30(16.9%)例发生再次骨折。Cox回归分析结果显示BALP、年龄、性别和BMD是患者再发骨折的独立影响因素。以BALP为预测标准,ROC曲线下面积为0.757,诊断临界点为29.0μg/L,灵敏度及特异度分别为84.3%、63.8%。Kaplan-Meier分析显示BALP29.0μg/L患者骨折再发率较BALP≤29.0μg/L更高(p=0.026)。结论骨质疏松骨折患者发生再骨折的风险较高,检测血清BALP水平是有效可行的预测指标。     

Effects of estrogen therapy on bone marrow adipocytes in postmenopausal osteoporotic women

Summary  One-year treatment of osteoporotic postmenopausal women with transdermal estrogen resulted in significant decreases in bone marrow adipocyte volume and prevented increases in adipocyte number as compared to placebo-treated controls. Estrogen treatment also prevented increases in mean adipocyte size over 1 year. Introduction  Aging is associated not only with bone loss but also with increases in bone marrow adipocytes. Since osteoblasts and adipocytes are derived from a common precursor, it is possible that with aging, there is a preferential “switch” in commitment of this precursor to the adipocyte over the osteoblast lineage. We tested the hypothesis that the apparent “age-related” increase in marrow adipocytes is due, at least in part, to estrogen (E) deficiency. Methods  Reanalysis of bone biopsies from a randomized, placebo-controlled trial involving 56 postmenopausal osteoporotic women (mean age, 64 years) treated either with placebo (PL, n = 27) or transdermal estradiol (0.1 mg/d, n = 29) for 1 year. Results  Adipocyte volume/tissue volume (AV/TV) and adipocyte number (Ad#) increased (by ∼20%, P < 0.05) in the PL group, but were unchanged (Ad#) or decreased (AV/TV, by −24%, P < 0.001) in the E group. E treatment also prevented increases in mean adipocyte size over 1 year. Conclusions  These findings represent the first in vivo demonstration in humans that not only ongoing bone loss, but also the increase in bone marrow adipocyte number and size in postmenopausal osteoporotic women may be due, at least in part, to E deficiency. Supported by NIH Grants AG004875 and AG028936.     

Bone histological heterogeneity in postmenopausal osteoporosis: A sequential histomorphometric study

We studied sequential bone biopsies performed at 6 to 24 month intervals from 14 untreated osteoporotic women (64 ± 7). Subgroups were defined, respectively, by increased osteoclastic resorption surfaces and decreased osteoblastic surfaces ± 2 S.D. Normal values were obtained from bone biopsy of 23 normal women (61 ± 8). When patients were divided into subgroups according to the above criteria the first biopsy showed that 3 out of the 14 patients had high resorption surfaces and 6 had low osteoblastic surfaces. Eight patients spontaneously changed during the study. In 2 patients there was a change in resorption surfaces, in 3 in osteoblastic surfaces and in 3 a change in both osteoblastic and resorption surfaces was observed. Considering the first or second bone biopsy results the patient variance was higher than the control subject's variance; however the variance between the first and second bone biopsy of one patient was not different from the variance inside the group of patients. The average intraindividual variation of the parameters on sequential biopsies was of the same order as the one we previously observed on simultaneous bone biopsies of normal and hemodialyzed patients. We concluded that if osteoporosis is a heterogeneous disorder, subgroups cannot be definitively defined on the basis of cellular parameters of bone remodelling assessed on bone biopsies.     

Alcohol alters whole body composition, inhibits bone formation, and increases bone marrow adiposity in rats

Summary  Chronic alcohol abuse is a risk factor for osteoporosis and sarcopenia, but the long-term effects of alcohol on the immature musculoskeletal system are less clear. The present investigation in growing rats was designed to determine the effects of alcohol consumption on body composition, muscle mass, and bone mass, architecture, and turnover. Introduction  Few studies have focused on the long-term effects of drinking on bone and muscle during skeletal maturation. Methods  Alcohol was included in the diet of 4-week-old male Sprague–Dawley rats (35% caloric intake) for 3 months. The controls were fed an isocaloric alcohol-free liquid diet ad libitum. A second study was performed in which the controls were pair-fed to the alcohol-fed animals. Results  Compared to ad libitum-fed age-matched controls, alcohol-fed rats weighed less and had lower lean mass, fat mass, and percent body fat. In addition, they had lower slow- and fast-twitch muscle mass, lower total body bone mineral content and bone mineral density, and lower cancellous bone volume in the lumbar vertebra and proximal tibia. The effects of alcohol consumption on body composition were reduced when compared to the pair-fed control diet, indicating that caloric restriction was a comorbidity factor. In contrast, the effects of alcohol to decrease bone formation and serum leptin and IGF-I levels and to increase bone marrow adiposity appeared independent of caloric restriction. Conclusions  The skeletal abnormalities in growing alcohol-fed rats were due to a combination of effects specific to alcohol consumption and alcohol-induced caloric restriction.     

Acute effects of deflazacort and prednisone on rates of mineralization and bone formation

The aims of this study were to determine (1) whether acute suppression of bone formation could be evaluated after the administration of corticosteroids in man by quantitative bone histomorphometry; and (2) whether there were significant differences between the effects of prednisone and its analog deflazacort. Thirteen patients who needed high-dose corticosteroid therapy were randomly allocated to two groups of treatment (prednisone or deflazacort). Quantitative bone histomorphometry, using the technique of triple labeling, and biochemical measurements of bone turnover were studied. There were no differences in biochemical indices of bone turnover between prednisone and deflazacort at the beginning and end of the 15 days of treatment course. During corticosteroid treatment, there were no significant changes in biochemical indices of bone turnover but a significant decline in total alkaline phosphatase (P<0.01). Histomorphometric indices, as revealed by measurements of tetracycline interval and extent of labeling, showed no significant differences in either mineral apposition rate or bone formation rate in the two groups. We conclude that the acute glucocorticoid suppression of bone turnover by glucocorticoids is not detectable within the first 2 weeks of treatment by histomorphometric techniques. No differences in bone effects of prednisone and deflazacort were detected in this short-term study.