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 marrow fat content in relation to bone remodeling and serum chemistry in intact and ovariectomized dogs

Summary It was previously shown that 11 months after ovariectomy the volume fraction of trabecular bone in the spine and 11th rib medullary canal of Beagle dogs (6 control, 9 ovariectomized) was significantly reduced. In this paper it is shown that these changes are accompanied by increased marrow fat volume in the 11th rib (59.0±9.5% vs. 44.3 ±10.0%). Conversely, the volume fraction of functional (hematopoietic) cells in the marrow was reduced by ovariectomy. Additionally, variations in marrow fat volume were tested for correlation with 22 other variables pertinent to bone physiology. Marrow fat volume was significantly positively correlated with serum osteocalcin, rib trabecular bone porosity, rib cross-sectional area, and gains in body weight. It was negatively correlated with serum estrogen concentrations and the extent of rib trabecular surfaces labeled with tetracycline.     

骨髓间充质干细胞移植对去卵巢骨质疏松骨量影响的实验研究

目的 探索骨髓间充质干细胞（BMSCs）移植对去卵巢骨质疏松大鼠骨密度的影响。方法 雌性SD大鼠随机分为空白对照组（A组）、模型组（B组）、细胞治疗组（C组）、雷诺昔芬药物治疗组（D组）。通过去卵巢建模成功后，C组通过尾静脉移植BMSCs，D组口服雷诺昔芬抗骨质疏松药物。结果 与A组相比，B组腰椎和股骨骨密度均明显降低（P＜0.01）。MSCs治疗后，C 组中的骨密度得到明显改善，并与B组比较具有统计学差异（P＜0.01），亦优于D组。结论 BMSCs可以有效改善去卵巢大鼠骨质，这为绝经后骨质疏松的治疗提供了一种新的方法，为进一步临床应用提供了实验支持。     

Increased trabecular bone density due to bone-loading exercises in postmenopausal osteoporotic women

Summary A program of diverse and dynamic loading exercises of the distal forearm, a common site of osteoporotic fractures, was applied three times a week for 5 months to 14 postmenopausal osteoporotic women. Two parameters were used to assess the effect of the exercises on bone mass. The mass density of bone (g/cm³) was measured by the Compton scattering technique. The bone mineral content (g/cm²) was measured by single photon absorptiometry. Both measurements were taken at the same location in the distal radius 1 year prior to the exercise period, at its beginning, and at its end, in both the exercised group and a matched control group of 25 osteoporotic women. During the exercise period the mean bone density decreased by 1.9% in the control group whereas it increased by 3.8% in the exercise group. The bone mineral content results did not demonstrate any significant trend over the whole period of the study. It is concluded that the trabecular bone tissue in the distal radius of postmenopausal osteoporotic women responds favorably to dynamic and diverse bone stressing exercises even in the seventh decade of life.     

绝经后妇女血清瘦素水平与骨代谢的关系

目的探讨绝经后妇女血清瘦素水平与骨代谢的关系.方法测定85例绝经妇女血清瘦素水平及体重指数、体脂量、甘油三脂和总胆固醇,用双能X线法测定股骨和腰椎的骨密度,并测定骨钙素及尿钙水平,分析瘦素与上述指标之间的相关性.结果用骨密度与瘦素及瘦素相关指标进行多元逐步回归分析,瘦素没有进入腰椎和股骨颈骨密度方程;瘦素与骨钙素及尿钙水平也均无相关.结论瘦素与绝经后妇女的骨代谢无直接关系.     

骨质疏松大鼠骨髓基质细胞膜片的体外构建研究

目的探讨骨质疏松大鼠骨髓基质细胞膜片的构建及基本生物学特性。方法建立大鼠绝经后骨质疏松症(PMOP)模型,分离培养骨质疏松大鼠骨髓基质细胞(O-r BMSCs),并以O-rBMSCs为种子细胞构建细胞膜片。通过倒置显微镜、HE染色、扫描电镜及透射电镜对细胞膜片进行形态学检测;以免疫组织化学染色检测细胞外基质相关蛋白的表达情况。结果成功建立了大鼠PMOP模型,体外分离培养的O-rBMSCs具有多向分化潜能。显微镜下可见细胞复层生长,采用富含维生素C的培养基连续培养10 d左右即可获得白色膜样结构,该细胞膜片具有较好的弹性,HE染色及扫描电镜观察发现O-rBMSCs膜片由多层细胞及丰富的细胞外基质组成。透射电镜下可观察到细胞间连接。免疫组织化学染色示O-rBMSCs膜片高表达Ⅰ型胶原、纤维连接蛋白。结论 O-rBMSCs体外采用富含维生素C的培养基连续培养可构建细胞膜片,该细胞膜片富含细胞外基质,有望应用于骨质疏松机体的组织再生。     

Metacarpal bone mass in normal and osteoporotic Japanese women using computed X-ray densitometry

The metacarpal bone mineral density (BMD) and metacarpal index (MCI) of the second metacarpal bone were measured by computed X-ray densitometry (CXD) (Teijin Ltd., Tokyo), which we have established with the development of microdensitometry of radiographs. In this study, we evaluated the basic attributes of this CXD method and determined the age-related changes in both metacarpal measurements in normal Japanese women. The precision in vivo was measured in eight subjects. The precision errors [coefficient of variation (CV)] were 0.2–1.2% CV for metacarpal BMD and 0.4–2.0% CV for MCI, respectively. We have obtained low precision error and more rapid analysis, within 3 minutes respectively, compared with the previous methods. Age-related changes in the metacarpal measurements were evaluated in 1438 normal women. Both measurements showed the most significant decrease in the sixth decade of life. The rate of decrease in the sixth decade was 1.6%/year for metacarpal BMD and 1.5%/year for MCI. On comparison between metacarpal BMD by CXD and spine BMD using dual energy X-ray absorptiometry (DXA) in 248 normal women with and without menstruation, the two measurements were found to be similarly decreased in the subjects within 5 years after menopause. There was also no significant difference in the Z-score between metacarpal BMD and spine BMD within 5 years after menopause. These results indicate that early postmenopausal bone loss occurs not only in the spine but also in the metacarpal bone. The metacarpal BMD for patients with osteoporosis was significantly lower than that for age-matched normal controls, although the Z-score for spine BMD (-1.46) was significantly better than that for metacarpal BMD (-0.82). In conclusion, because CXD has excellent low precision error and is widely available at relatively low cost, it appears potentially to be applicable to problems in the diagnosis and management of osteoporosis, when used in association with DXA.     

绝经后骨质疏松症妇女血清痩素水平与骨密度的关系

目的 观察绝经后骨质疏松症妇女血清瘦素水平与骨密度(BMD)、骨矿含量(BMC)的相关性。方法 ELISA法检测32名绝经后骨质疏松症妇女(绝经组)和27名体重指数(BMI)相匹配的非绝经正常对照者(非绝经组)的空腹血清瘦素浓度,双能X线骨密度仪测定受试者腰椎BMD、BMC、T值、Z值。结果 绝经组和非绝经组的血清瘦素浓度分别为12.43±7.90ng/ml和11.76±4.42ng/ml,两组之间无差异;两组血清瘦素浓度均与体重、BMI和脂肪含量(Fat％)显著正相关,绝经组的瘦素水平与BMD及BMC无相关性,非绝经组瘦素浓度与BMDIL3和BMCL5相关(r=0.132,P<0.05;r=0.140,P<0.05),但调整BMI后瘦素浓度与BMD及BMC:的相关性消失(r=0.079,P>0.05;r=0.067,P>0.05)。结论成年妇女瘦素水平与体重、体脂及脂肪含量显著相关,瘦素不是绝经后妇女骨质疏松症的主要影响因素。     

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。     

The relationship between bone mineral density and ultrasound in postmenopausal and osteoporotic women

The aim of this cross-sectional study was to use a novel method of data analysis to demonstrate that patients with osteoporosis have significantly lower ultrasound results in the heel after correcting for the effect of bone mineral density (BMD) measured in the spine or hip. Three groups of patients were studied: healthy early postmenopausal women, within 3 years of the menopause (n=104, 50%), healthy late postmenopausal women, more than 10 years from the menopause (n=75, 36%), and a group of women with osteoporosis as defined by WHO criteria (n=30, 14%). Broadband ultrasound attenuation (BUA), speed of sound (SOS) and Stiffness were measured using a Lunar Achilles heel machine, and BMD of the lumbar spine and left hip was measured using dual-energy X-ray absorptiometry (DXA). SOS, BUA and Stiffness were regressed against lumbar spine BMD and femoral BMD for all three groups combined. The correlation coefficients were in the range 0.52–0.58, in agreement with previously published work. Using a calculated ratio R, analysis of variance demonstrated that the ratio was significantly higher in the osteoporotic group compared with the other two groups. This implied that heel ultrasound values are proportionately lower in the osteoporotic group compared with the other two groups for an equivalent value of lumbar spine and femoral neck BMD. We conclude that postmenopausal bone loss is not associated with different ultasound values once lumbar spine or femoral neck BMD is taken into account. Ultrasound does not give additional information about patterns of bone loss in postmenopausal patients but is important in those patients with osteoporosis and fractures.     

The relationship between osteoarthritis of the hands,bone mineral density,and osteoporotic fractures in elderly women

To study the relationship between osteoarthritis (OA) and osteoporosis (OP), radiographic osteoarthritis lesions of the hands (HOA) were quantified in 300 healthy women, aged 75 years or more, as a subgroup of a cohort originally recruited for a multi-centre study of risk factors for femoral neck fracture. The HOA combined score (i.e. the sum of the grades of joint-space narrowing, osteophytes, erosions and joint misalignment), the osteophytosis score and the joint-space narrowing score were calculated on a radiograph of both hands. Bone mineral density (BMD) was measured using dual-energy X-ray absortiometry (Lunar DPX) at the femoral neck, Ward's triangle and the total body. BMDs of the total spine, lumbar spine, and the upper and lower limbs were derived from the regional analyses of the total body measurement. Correlations between bone mass, HOA scores and other variables were explored by multiple linear regression and stepwise logistic regression analysis. The HOA combined score was positively correlated with increasing age but not with body mass index. In the multiple regression analyses the HOA combined score positively correlated with BMD at all sites, except the femoral neck and Ward's triangle; the osteophytosis score correlated with BMD at all sites; and no correlation was found between BMD and the joint-space narrowing score. According to stepwise logistic regression and after adjustment of BMD for age, women with an HOA combined score higher than 20 had signficantly higher BMD values at all skeletal sites. Sixty-nine women (23%) reported a history of osteoporotic fracture; among them, 20 (6.6%) reported a history of vertebral fracture. The OA score of both subgroups was significantly lower than that of women with no history of fracture. These data suggest that in elderly women the severity of HOA is positively correlated with bone mass and that women with a high score of HOA more rarely report a history of osteoporotic fracture.     

绝经后女性股骨近端骨密度与骨质疏松性骨折相关性研究

目的：研究绝经后女性股骨近端骨密度的变化规律与骨质疏松症、骨质疏松性骨折间的关系。方法采用法国Medlink公司Osteocore 3型双能X线骨密度仪,对本地区417例绝经后女性股骨颈、大转子、粗隆间、全髋进行骨密度测定。结果骨折组各年龄段、各部位的BMD均比非骨折组低（ P＜0．05）。随着年龄的增长,股骨近端骨量逐渐丢失,除了45～50组,其余各年龄段骨折组的患病率明显高于非骨折组（ P＜0．05）,骨密度值越低,骨折危险性越大。结论绝经后女性股骨近端骨密度与发生骨质疏松性骨折的风险呈明显负相关性,应该注意预防。     

雌激素对去势骨质疏松症大鼠骨密度和骨代谢影响的实验研究

目的研究雌激素对去势骨质疏松症模型大鼠骨密度(bone mineral density,BMD)和骨代谢的影响,并探讨其治疗骨质疏松症的机制。方法将48只雌性SD大鼠随机分配成对照组、模型组、雌激素组和雌激素+三苯氧胺组,每组12只。除对照组外,其他各组大鼠采用双侧卵巢摘除法制备骨质疏松症模型。雌激素组给予尼尔雌醇(1 mg/kg)灌胃,1次/周;雌激素+三苯氧胺组给予尼尔雌醇(1 mg/kg)和三苯氧胺(3 mg/kg)灌胃,1次/周;对照组和模型组分别使用等量生理盐水灌胃,均持续3个月。3个月后取材,检测大鼠左侧股骨BMD和股骨骨矿物盐含量、血清钙含量以及胫骨中骨骼钙含量;酶联免疫法检测大鼠血清碱性磷酸酶(alkaline phosphates,ALP)、血清抗酒石酸酸性磷酸酶-5b(tartrate resistant acid phosphatase-5b,TRAP-5b)的含量;免疫组化检测大鼠胫骨中骨保护素(osteoprotegerin,OPG)和核因子κB受体活化因子配体(receptor activator for nuclear factor-κB ligand,RANKL)蛋白的表达情况。结果治疗前,与对照组比较其他各组血清钙含量和血清TRAP-5b含量均显著升高(P0.05),骨钙含量、BMD和骨矿物盐含量显著降低(P0.05),血清ALP含量无显著性变化(P0.05);治疗后,与模型组比较雌激素组血清钙含量、血清TRAP-5b含量以及胫骨组织RANKL蛋白表达均显著降低(P0.05),骨钙含量、血清ALP含量、BMD、骨矿物盐含量以及胫骨组织OPG蛋白表达均显著升高(P0.05),而治疗后,与模型组比较雌激素+三苯氧胺组各项指标变化差异无统计学意义(P0.05)。结论雌激素通过显著性提高去卵巢骨质疏松模型大鼠骨骼钙、ALP、股骨骨密度、骨矿物盐以及OPG的含量,抑制骨钙流失、TRAP-5b及RANKL蛋白表达,达到改善骨质疏松的作用。     

骨髓基质干细胞成脂分化的调控及其对骨质疏松的影响

研究发现随着年龄的增长和绝经期后骨质疏松,骨髓腔内的脂肪细胞逐渐增多,取代了成骨细胞,因此抑制骨髓基质干细胞成脂分化是目前治疗骨质疏松的新途径。应用各种成脂诱导剂建立体外定向诱导骨髓基质干细胞成脂分化模型是研究新途径的基础。除了通过光学显微镜观察成脂分化的能力,还可运用分子生物学的方法定性、定量检测成脂分化的程度。过氧化物酶增殖子激活受体(PPARγ)是脂肪细胞的分化过程中起关键性作用的调节因子,组蛋白去乙酰化酶(SIRT1)被激活后能抑制PPARγ的表达,减少脂肪细胞的生成,起到预防和治疗骨质疏松的作用。笔者就以上方面和对减少骨髓脂肪分化的策略作了综述。     

老年骨质疏松女性髋部骨密度、骨转换指标与血脂、血清尿酸相关性研究

目的研究老年骨质疏松女性髋部骨密度(bone mineral density,BMD)与血清总胆固醇(total cholesterol,TC)、血清甘油三酯(triglyceride,TG)、血清高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、血清低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)和血清尿酸(uric acid,UA)的相关性。方法收集2014年1月1日至2015年12月31日就诊的老年女性骨质疏松患者108例。记录患者的年龄、身高、体重、股骨颈BMD、股骨大转子BMD、股骨粗隆间BMD、髋部整体BMD、Ward’s区BMD、TC、TG、HDL-C、LDL-C、UA、血清I型胶原交联C末端肽(C-terminal crosslinking telopeptide of type I collagen,CTX)、I型原胶原N-端前肽(procollagen type I N propeptide,PINP)、25羟基维生素D(25-OH-Vit D,Vit D-T)及基础疾病情况等资料。髋部BMD、体质量指数(body mass index,BMI)、β-CTX、PINP、Vit D-T、TC、TG、LDL-C、HDL-C、UA相关性检验采用Pearson相关性检验。结果股骨颈BMD与年龄、β-CTX呈负相关,与BMI、Vit D-T、TG、UA呈正相关(r0,P0.05)。股骨大转子BMD与年龄、β-CTX呈负相关(r0,P0.05),与BMI、Vit D-T、TC、TG、LDL-C、UA呈正相关(r0,P0.05)。股骨粗隆间BMD与年龄、β-CTX、PINP呈负相关(r0,P0.05),与BMI、Vit D-T、TC、TG、UA呈正相关(r0,P0.05)。髋部整体BMD与与年龄、β-CTX呈负相关(r0,P0.05),与BMI、Vit D-T、TC、TG、LDL-C、UA呈正相关(r0,P0.05)。股骨Ward’s区BMD与年龄、β-CTX呈负相关(r0,P0.05),与BMI、Vit D-T、TC、LDL-C、UA呈正相关(r0,P0.05)。TC与β-CTX、PINP呈负相关(r0,P0.05),与Vit D-T、UA呈正相关(r0,P0.05)。TG与UA呈正相关(r0,P0.05)。HDL-C与Vit D-T、UA呈正相关(r0,P0.05)。LDL-C与β-CTX、PINP呈负相关(r0,P0.05),与Vit D-T、UA呈正相关(r0,P0.05)。结论骨质疏松患者髋部不同部位骨密度与血脂的相关性不同,适当水平的血清总胆固醇及尿酸有利于维持骨量,预防低骨量及骨质疏松的发生。     

股骨颈强度指数及骨髓脂质在评价骨质疏松性髋部骨折中的作用

目的探讨股骨颈强度指数(FSI)及骨髓脂质分数(LF)在预测股骨颈脆性骨折风险中的价值。方法女性股骨颈骨折患者17例及正常对照组68例行DXA扫描获取股骨颈骨密度(FN_BMD)及FSI,MRS扫描获取LF。Bayes法建立股骨颈骨折判别方程,比较FSI及LF骨折风险判别效果。结果 LF与FN_BMD(r=-0.581)、FSI(r=-0.408)呈中度负相关(P均0.05)。校正年龄、身高、体重、BMI,LF与FN_BMD、FSI相关性依然存在。校正上述混杂因素,骨折组FSI(1.10±0.16)较正常对照组(1.37±0.25)低,LF(79.2±16.4%)较对照组(57.9±16.8%)高(P均0.05)。校正FN_BMD,FSI、LF在组间仍存在统计学差异。包含LF判别方程对骨折判别的敏感性、特异性分别为74.7%、68.4%,准确率为68.2%(自身回代法)、65.9%(交互校验法);包含FSI判别方程对骨折判别的敏感性、特异性分别为79.7%、76.9%,准确率为76.5%、72.9%。结论LF及FSI独立于BMD决定髋部骨强度的有用因子,MRS测定LF对预测髋部脆性骨折有一定价值。     

酒精性骨质疏松症造模鼠的骨与生化代谢特征

目的:观察酒精中毒引发骨质疏松造模鼠的骨与生化代谢变化特征,探讨酒精对骨质疏松症形成过程的毒性作用。方法:SD大鼠120只分为3组,实验组A给予45°白酒8ml·kg-1·d-1,每天2次灌胃,实验组B给予45°白酒6ml·kg-1·d-1,每天2次灌胃,对照组以8ml生理盐水灌胃,分别于8、16、24周取材,进行相关骨代谢指标的测定。结果:各实验组动物骨小梁稀疏,髓腔脂肪细胞增大、增多;骨细胞数量减少,退变固缩或出现脂滴,成骨细胞减少,尤其实验组A改变最为明显。16周后实验组A的BMD显著下降;24周后骨Ca、HOP含量及Ca/HOP比值均呈显著降低;血清AKP、BGP、血Ca及钙磷乘积显著下降;而尿Ca、P、HOP排泄量则呈显著增多。结论:酒精中毒可引起模鼠骨代谢紊乱,继发骨质疏松。     

Regional variations in histomorphometric bone dynamics from the skeleton of an osteoporotic woman

Summary Histomorphometric evaluation of bone formation in an intravital tetracycline-labeled skeleton of a suddenly deceased osteoporotic woman is presented. The 24 skeletal sites investigated displayed substantial regional variations which, for two out of four cortical bone dynamics and all trabecular bone dynamics, were significantly higher than the intraspecimen variation. Poor agreement was found between bone formation in left- and right-sided iliac crest specimens. Furthermore, no agreement was found between trabecular bone formation and amount of hematopoetic marrow. With all the limitations that the study of a single patient involves it is suggested that (1) bone biopsy in individual patients should not be the only basis for therapeutic decisions in postmenopausal osteoporosis; (2) amount of hematopoietic marrow does not seem to influence bone formation; and (3) bone formation in the skeleton display large regional variations, which are larger for the fraction of labeled surfaces than for appositional rate.     

Relationship between bone fluoride content and histological evidence of calcification defects in osteoporotic women treated long term with sodium fluoride

Fluoride treatment is used to increase bone formation and cancellous bone mass in patients suffering from postmenopausal osteoporosis with vertebral fractures. Patients submitted to similar therapeutic protocols have shown various histological responses to the treatment, some developing calcification defects and others not. In fact, the bone histological response to fluoride salts depends on the cumulative uptake of fluoride by bone. To clarify the relationship between the presence of calcification defects (identified by the presence of mottled bone and linear formation defects) and the bone fluoride content, a retrospective study was performed on 29 women with type 1 osteoporosis and treated for several months (11–24) with sodium fluoride (50 mg/day), calcium and vitamin D. Bone fluoride content always significantly increased after treatment, but it was significantly higher in patients showing calcification defects than in those having no defects. These differences between the two groups of patients were not due to differences in clinical details (no significant differences concerning age, duration of treatment, total amount of fluoride ingested, renal function) or in their bone remodelling activity. Thus, it may be hypothesized that the high bone fluoride uptake is due to different individual responses from one patient to another concerning the bioavailability of the same dose of fluoride. This is difficult to predict, except by testing the individual bioavailability of the compound to be used in each patient before starting long-term treatment.