Bone mineral density, osteopenia, and osteoporosis in the rhesus macaques of Cayo Santiago

This cross-sectional study investigates metabolic bone disease and the relationship between age and bone mineral density (BMD) in males and females of a large, well-documented skeletal population of free-ranging rhesus monkeys (Macaca mulatta), from the Caribbean Primate Research Center Museum collection from Cayo Santiago, Puerto Rico. The sample consists of 254 individuals aged 1.0-20+ years. The data consist of measurements of bone mineral content and bone mineral density, obtained from dual-energy X-ray absorptiometry (DEXA), of the last lumbar vertebra from each monkey. The pattern of BMD differs between male and female rhesus macaques. Females exhibit an initial increase in BMD with age, with peak bone density occurring around age 9.5 years, and remaining constant until 17.2 years, after which there is a steady decline in BMD. Males acquire bone mass at a faster rate, and attain a higher peak BMD at an earlier age than do females, at around 7 years of age, and BMD remains relatively constant between ages 7-18.5 years. After age 7 there is no apparent effect of age on BMD in the males of this sample; males older than 18.5 years were excluded due to the presence of vertebral osteophytosis, which interferes with DEXA. The combined frequency of osteopenia and osteoporosis in this population is 12.4%. BMD values of monkeys with vertebral wedge fractures are generally higher than those of virtually all of the nonfractured osteopenic/osteoporotic individuals, thus supporting the view that BMD as measured by DEXA is a useful but imperfect predictor of fracture risk, and that low BMD may not always precede fractures in vertebral bones. Other factors such as bone quality (i.e., trabecular connectivity) should also be considered. The skeletal integrity of a vertebra may be compromised by the loss of key trabeculae, resulting in structural failure, but the spine may still show a BMD value within normal limits, or within the range of osteopenia.     

Effect of parity on bone mineral density in female rhesus macaques from Cayo Santiago

This cross-sectional study investigates the relationship between parity, bone mineral density, and spontaneous osteopenia/osteoporosis in a large skeletal population of female rhesus macaques (Macaca mulatta) from the free-ranging colony of Cayo Santiago, Puerto Rico. The sample consists of 119 mature female monkeys aged 4.0-22.2 years at time of death. The data consist of measurements of bone mineral content (BMC) and bone mineral density (BMD), obtained from dual-energy X-ray absorptiometry (DEXA) of the last lumbar vertebra. After controlling for age, there is a significant increase in BMD of the spine with increasing parity (P = 0.0006), up to a parity of 7 offspring. Thus, high parity initially has a positive effect on BMD in female rhesus monkeys, but this positive effect disappears with parities that are greater than 7 offspring. After controlling for parity, however, age has a negative (P = 0.015) effect on BMD, beginning several years after the attainment of peak BMD (age 9.5 years). Thus, it appears that parity initially mitigates the effects of aging, but the positive effect of parity on BMD is eventually overwhelmed by the aging process. Mean BMC and BMD values are higher in parous females compared to nulliparous females in the same age range. Similarly, females with low parity have significantly lower mean BMD values than do age-matched high-parity controls, and the frequency of osteopenia and osteoporosis is greater in low-parity females. Forty-three percent (43%) of the osteopenic/osteoporotic females in the sample are members of the low-parity group, even though it composes only 13% (16/119) of the entire sample. This study demonstrates that the free-ranging female rhesus monkeys from Cayo Santiago are a good nonhuman primate model for the study of bone mineral density, parity, osteopenia, and osteoporosis.     

Spatial distribution of trabeculae in iliac bone from 145 osteoporotic females

145 women showing clinical and radiological signs of involutional osteoporosis of the spine were biopsed at the ilium for histomorphometric analysis of bone mass including trabecular bone volume and parameters reflecting the spatial distribution of bony elements (mean trabecular plate thickness, density and separation). Results were compared with an age-matched population of 22 healthy females. Postmenopausal osteoporotics (i.e. younger than 75 years) were characterized by a significant reduction in trabecular bone volume, plate density and thickness, while senile osteoporotics (i.e. older than 75 years) did not exhibit any difference with controls. 51% of the osteoporotic patients had a trabecular bone volume higher than the spontaneous vertebral crush threshold defined by Meunier. Osteoporotic patients with trabecular bone volume under the vertebral crush threshold had a significant decrease in all trabecular parameters. On the opposite, patients with trabecular bone volume above the vertebral crush threshold had only a significant decrease in the number of trabeculae. A negative correlation was found between age and plate density in both osteoporotic patients and controls. A linear correlation was found between trabecular bone volume and plate density, but thickness and density of trabecular plates were not correlated. This study confirms that involutional osteoporosis is not only a decreased bone mass disorder. A modified spatial distribution of trabeculae or a mechanically less resistant bone matrix could be additional factors.     

Adiponectin is a negative regulator of bone mineral and bone strength in growing mice

Obesity is associated with increased bone mineral density (BMD) but the mechanism for this is unclear. Serum levels of the adipokine adiponectin are inversely correlated with obesity, but results from studies on its relationship to bone mass are conflicting. The objective of this study was to compare bone mineral content (BMC), BMD and biomechanical strength properties of femur and lumbar vertebrae in 8- and 16-week old adiponectin transgenic mice (AdTg). These mice exhibit significantly elevated circulating adiponectin but have similar body weights compared to wild-type (WT) littermates that were used as controls. Female AdTg mice displayed significantly lower femur BMC at 8 and 16 weeks of age and femur neck peak load was significantly lower in 8-week old AdTg mice of both genders compared to controls. The peak load from compression testing of an individual lumbar vertebra was significantly lower in female AdTg mice compared to WT at 8 weeks, and this difference persisted at 16 weeks of age. In addition, lumbar vertebrae BMC was significantly lower in 16-week old male AdTg mice compared to WT although vertebra peak load was not different. Serum adiponectin levels were inversely correlated with femur BMC. In summary, elevated circulating adiponectin inhibits the acquisition of bone mass in growing mice and results in decreased biomechanical measures of functional strength that are surrogate measures of susceptibility to fractures. These results support a role for circulating adiponectin as a metabolic link that can explain, at least in part, the positive relationship between obesity and both bone mass and reduced susceptibility to fractures.     

Trabecular bone modulus-density relationships depend on anatomic site

One outstanding issue regarding the relationship between elastic modulus and density for trabecular bone is whether the relationship depends on anatomic site. To address this, on-axis elastic moduli and apparent densities were measured for 142 specimens of human trabecular bone from the vertebra (n=61), proximal tibia (n=31), femoral greater trochanter (n=23), and femoral neck (n=27). Specimens were obtained from 61 cadavers (mean+/-SD age=67+/-15 years). Experimental protocols were used that minimized end-artifact errors and controlled for specimen orientation. Tissue moduli were computed for a subset of 18 specimens using high-resolution linear finite element analyses and also using two previously developed theoretical relationships (Bone 25 (1999) 481; J. Elasticity 53 (1999) 125). Resultant power law regressions between modulus and density did depend on anatomic site, as determined via an analysis of covariance. The inter-site differences were among the leading coefficients (p<0.02), but not the exponents (p>0.08), which ranged 1.49-2.18. At a given density, specimens from the tibia had higher moduli than those from the vertebra (p=0.01) and femoral neck (p=0.002); those from the trochanter had higher moduli than the vertebra (p=0.02). These differences could be as large as almost 50%, and errors in predicted values of modulus increased by up to 65% when site-dependence was ignored. These results indicate that there is no universal modulus-density relationship for on-axis loading. Tissue moduli computed using methods that account for inter-site architectural variations did not differ across site (p>0.15), suggesting that the site-specificity in apparent modulus-density relationships may be attributed to differences in architecture.     

Noninvasive markers of bone metabolism in the rhesus monkey: Normal effects of age and gender

Abstract: Measurement of bone turnover in conditions such as osteoporosis has been limited by the need for invasive iliac bone biopsy to reliably determine parameters of bone metabolism. Recent advances in the area of serum and urinary markers of bone metabolism have raised the possibility for noninvasive measurements; however, little nonhuman primate data exist for these parameters. The purpose of this experiment was to define the normal range and variability of several of the newer noninvasive bone markers which are currently under investigation in humans. The primary intent was to determine age and gender variability, as well as provide some normative data for future experiments in nonhuman primates. Twenty-four rhesus macaques were divided into equal groups of male and female according to the following age groupings: 3 years, 5–10 years, 15–20 years, and > 25 years. Urine was collected three times daily for a four-day period and measured for several markers of bone turnoverm including pyridinoline (PYD), deoxypyrodinoline (DPD), hydroxyproline, and creatinine. Bone mineral density measurements of the lumbar spine were performed at the beginning and end of the study period. Serum was also obtained at the time of bone densitometry for measurement of osteocalcin levels by radioimmunoassay. There were no significant differences in bone mineral density, urine PYD, or urine DPD based on gender. Bone density was lowest in the youngest animals, peaked in the 15–20-year group, but again decreased in the oldest animals. The osteocalcin, PYD, and DPD levels followed an inversely related pattern to bone density. The most important result was the relative age insensitivity of the ratio of PYD:DPD in monkeys up to age 20 years. Since bone density changes take months or years to become measurable and iliac biopsies are invasive, the PYD/DPD marker ratio may have important implications for rapid noninvasive measurement of the effects of potential treatments for osteoporosis in the non-human primate model.     

Relationship between serum albumin and bone mineral density in postmenopausal women and in patients with hypoalbuminemia.

Some discrepancies exist about the relationship between serum albumin level and the pathogenesis of osteoporosis; moreover, most of the studies available have especially concerned patients with osteoporosis, often associated with fractures. Our study, therefore, aims to investigate the presence of a relationship between serum albumin level and bone mineral density in a group of healthy women (n=650; mean age 59.0 +/- 7.4 years) who voluntarily underwent screening for osteoporosis only because they were menopausal (11.2 +/- 7.4 years since menopause) and, for comparison, in a group of outpatients (n = 44; mean age 57.6 +/- 7.0 years; 9.1 +/- 6.7 years since menopause) with hypoalbuminemia associated with diseases. The results show a lack of any relationship in healthy women between serum albumin value and bone mineral density; the lack of correlation was also shown when the postmenopausal women were down into normal, osteopenic and osteoporotic (WHO criteria) or in hypo, normal and hyperalbuminemic. The only significant parameters associated with lower bone mineral density, in fact, were age and years since menopause (p<0.0001 and p<0.0001 respectively at lumbar spine and p<0.02 and p<0.001 at femoral neck level). In the group of patients with hypoalbuminemia associated with diseases, on the other hand, a relationship between reduced bone mineral density and hypoalbuminemia was found (p<0.01 and p<0.05 respectively at lumbar spine and femoral neck). In conclusion, in healthy postmenopausal women the serum albumin level does not play a significant role in the pathogenesis of bone density reduction, which is mainly due to the number of years since menopause and advancing age. The hypoalbuminemia may be related to the reduction of bone mass only in the subjects affected by diseases associated with a significant albumin reduction.     

0～3岁婴幼儿超声骨密度现状调查及影响因素分析

目的:了解0~3岁婴幼儿的骨密度现状,并分析其相关影响因素,为婴幼儿骨密度不足的预防工作提供依据。方法:选取2016年1月-2018年10月期间于我院进行健康体检的0~3岁婴幼儿860例为研究对象。采用超声骨密度测量仪对入选婴幼儿左腿胫骨中段骨密度进行检测,并对婴幼儿的骨密度现状进行分析。采用问卷调查方式收集所有婴幼儿的性别、年龄、喂养方式、是否补充维生素D、户外活动时间等资料,并采用单因素和多因素Logistic回归分析0~3岁婴幼儿骨密度的影响因素。结果:860例婴幼儿中,骨密度正常婴幼儿336例,轻度骨密度不足婴幼儿196例,中度骨密度不足婴幼儿179例,重度骨密度不足婴幼儿149例,骨密度不足发生率为60.93%。单因素分析结果显示,不同年龄、性别、是否补充维生素D及不同户外活动时间婴幼儿之间的骨密度不足发生率比较差异有统计学意义(P0.05),而不同喂养方式婴幼儿之间的骨密度不足发生率比较差异无统计学意义(P0.05)。多因素Logistic回归分析结果显示,年龄(0~6个月,7~12个月)、性别(女)、补充维生素D(否)、户外活动时间(1 h)为0~3岁婴幼儿骨密度的危险因素(P0.05)。结论:0~3岁婴幼儿的骨密度不足发生率较高,年龄、女性、未补充维生素D、户外活动时间过少均是0~3岁婴幼儿骨密度的危险因素,可通过适量补充维生素D、增加户外活动时间以提高婴幼儿骨密度值。     

The effect of primary lack of estrogens and the influence of the age at the beginning of estrogen therapy on bone mineral density in patients with Turner's syndrome

Lumbar spine bone mineral density (BMD) values were measured in women with Turner's syndrome (TS) and the influence of primary ovarian failure as well as the age at the start of estroprogestins (EP) therapy were considered. EP treatment with 2mg of estradiol (E2) and BMD monitoring were started in 72 and finally continued for 5 years in 34 patients with TS, aged 12-38 years, previously not treated with growth hormone or anabolic steroids. The mean total BMD gain (deltaBMD) was 20% and the most significant increase was observed after the first (7.5%) and the second (6.6%) year of the therapy. Before the start and during EP treatment E2 levels were evaluated: they increased from 9.2pg/ml to the values observed in the controls (C) but positive correlation with BMD was not observed. Analysis of TS patients in age brackets (<15 years, 15-20 years, 21-25 years, >25 years) showed that only in the group that started EP treatment before the age of 15 every year significant deltaBMD was observed. The group that started EP therapy after the age of 20 didn't achieve significant deltaBMD. Patients wit TS had significantly higher levels of bone metabolism markers (Ntx and BALP) than the controls and in both groups negative correlation with age was found. On the basis of the results the conclusion was made that in hypoestrogenic women, not exclusively TS, the age when estrogen therapy is started may determine the effects in relation to bone mass. The administered E2 doses may also be important.     

Temporal and geographical variation in skeletal fluoride content of roe deer (Capreolus capreolus) from industrialized areas in Germany

In order to study temporal and spatial variation of environmental fluoride levels, we analyzed the mandibular bone fluoride content of 157 roe deer (age range: 1-11 years) from two industrialized regions (Ruhr area: n = 76, sampling period 1955-1998; area W of Cologne: n = 81, sampling period 1983 1998) in the federal state of North Rhine-Westphalia, Germany. Bone fluoride values (dry weight basis) ranged between 150 mg F/kg (2 year-old specimen taken in 1997) and 5724 mg F/kg (10 year-old specimen taken in 1957). In both study areas, a pronounced decline in mandibular bone fluoride concentrations occurred over the respective sampling periods. In consequence, bone fluoride content of animals (both study areas pooled) taken during the period 1990-1998 was significantly (P < 0.00001) lower than that of roe deer from the period 1955 1989, while the two animal groups did not significantly differ in age. These findings are regarded as indicative of a considerable reduction of fluoride deposition into the animals' habitats, due to effective emission control measures. Bone fluoride values for the period 1990-1998 in the roe deer from the Ruhr area significantly (P < 0.005) exceeded those of the individuals from the study area W of Cologne, while the difference in age between the two groups was not significant. In both study areas, a significant (P < 0.00001) positive correlation between age and mandibular bone fluoride content (Ruhr area: rs = 0.601; area W of Cologne: rs = 0.725) was found for animals taken during this period. The present study underscores the suitability of analyzing skeletal fluoride concentrations in wild roe deer in order to monitor the magnitude of environmental contamination by fluoride and thereby to assess the efficiency of measures taken to reduce fluoride emissions from industrial sources.     

Nuclear medicine studies of aging—VII. Humeral deltoid tuberosity on bone scans and radiographs

Because of the occasional finding of increased deposition of bone imaging agent in the area of the humeral deltoid tuberosity, we analyzed both bone scans and radiographs to determine if there were age related correlations. Only 29% of patients of age 35 years or younger showed any radiographie evidence of deltoid tuberosity. This increased to 48% in the 36–64 y age group (and 46% in those of age 65 y and above). Bone scans (^99mTc-MDP) of the humerus showed that 26% of individuals of ages 20–39 y had increased uptake in the deltoid tuberosity area. The figure was 21% of those in the 85–94 y age group. However, distribution between sexes in the 20–39 y age cohort was asymmetric (44% of males showed the bone scan finding, but only 15% of the females). We then reviewed cases that had shown the most prominent deltoid tuberosity on humeral radiographs. Thirteen of the 14 cases (93%) were males. Deposition of bone imaging agent in the deltoid tuberosity region was thus only slightly correlated with age (more common after age 35 y), but strongly correlated with sex (males more common) in all three major age groups (35 and under, 36–64, and 65 years and over). Possible interrelations with bone size and muscle mass were pointed out.     

Estimation of bone matrix apparent stiffness variation caused by osteocyte lacunar size and density

The role of osteocyte lacunar size and density on the apparent stiffness of bone matrix was predicted using a mechanical model from the literature. Lacunar size and lacunar density for different bones from different gender and age groups were used to predict the range of matrix apparent stiffness values for human cortical and cancellous tissue. The results suggest that bone matrix apparent stiffness depends on tissue type (cortical versus cancellous), age, and gender, the magnitudes of the effects being significant but small in all cases. Males had a higher predicted matrix apparent stiffness than females for vertebral cancellous bone (p< I0(-7)) and the difference increased with age (p =0.0007). In contrast, matrix apparent stiffness was not different between males and females forfemoral cortical bone and increased with age in both males (p < 0.0001) and females (p < 0.0364). Osteocyte lacunar density and size may cause significant gender and age-related variations in bone matrix apparent stiffness. The magnitude of variations in matrix apparent stiffness was small within the physiological range of lacunar size and density for healthy bone, whereas the variations can be profound in certain pathological cases. It was proposed that the mechanical effects of osteocyte density be uncoupled from their biological effects by controlling lacunar size in normal bone.     

Heritability of bone mass: a longitudinal study in aging male twins

Midshaft radial bone mass was first measured from 1970 through 1972 by photon absorptiometry in 42 pairs of monozygotic (MZ) and 38 pairs of dizygotic (DZ) male Caucasian twins (age 44-55 years). The MZ intraclass correlation (rMZ) of .70 was significantly larger (P less than .05) than the DZ correlation (rDZ) of .45, providing evidence for genetic influences (Smith et al. 1973). Radial bone mass measurements repeated 16 years later (1986-87) on 25 of the MZ pairs and on 21 of the DZ pairs revealed an rMZ of .61 and an rDZ of .44, but the difference was not significant (P greater than .05). The twins had an average radial mass loss of 0.49%/year between the two examinations. The rMZ (.52) and rDZ (.49) values for the 16-year loss in radial mass were both significantly different from zero, but their similar size indicated that the correlations were due to nongenetic factors. In a search for the source of genetic influences on adult radial mass, heritability was estimated by the formula 2(rMZ - rDZ) for radial width and was found to be .66 and .76 (P less than .05) for examinations 1 and 2, respectively. An index of radial density (mass/width) was calculated, and the differences between rMZ and rDZ were not significant at either examination. The intraclass correlations (rMZ = .35; rDZ = .43) were both significant for the loss of bone density between examinations but provided no evidence for genetic influences, results similar to the findings for the loss of mass.(ABSTRACT TRUNCATED AT 250 WORDS)     

Constructive effect of exogenous melatonin against osteoporosis after ovariectomy in rats

OBJECTIVE: To analyze histomorphometric, densitometric and biochemical effects of melatonin on osteoporosis in ovariectomized rats. STUDY DESIGN: Wistar rats were divided into 6 groups. Group C: control; Group I: bilateral ovariectomy (OVX); Group II: OVX + vehicle; Group III: OVX + 10 mg/kg/day melatonin (MLT); Group IV: OVX + 30 mg/kg/day MLT; Group V: sham + 10 mg/kg/day MLT. Cortex, trabecula, osteoblast and osteoclast numbers were evaluated on vertebra and femur histomorphometrically. Hydroxyproline analysis was used to determine collagen content of femur and vertebrae. Bone mineral density and bone mineral content were measured. RESULTS: Trabecular thickness and trabecular area of vertebra and femur and cortical thickness of femur showed remarkable decrease after OVX, but increased after MLT treatment in the OVX+MLT groups. Following OVX, no statistically significant difference was found in number of osteoblasts or osteoclasts, trabecular number or levels of hydroxyproline after treatment with MLT. OVX caused significant decrease in bone mineral density, but treatment with MLT was unable to reverse this effect. CONCLUSION: MLT may trigger microscopic changes in bone, and time of application is critical for clinical recovery. It can be effective in helping treat postmenopausal osteoporosis. However, it is contraindicated in women who have normal-functioning ovaries.     

Standardized data and relationship between bone growth and bone metabolism in female G?ttingen minipigs.

Minipigs have been studied as a model of osteoporosis. However, little information is available regarding their bone physiology. We established standardized bone data and investigated the relationship between bone growth and bone metabolism in female minipigs. Blood and urine samples were obtained from 53 female G?ttingen minipigs, 3-76 months of age, for measurement of bone biomarkers (i.e., BAP, OC, NTX, and DPD). The lumbar vertebra and femur were excised to determine the growth plate condition, bone length, bone mineral content (BMC), and bone mineral density (BMD). High levels of bone biomarkers were observed during the initial period after birth, decreasing thereafter with age. Bone biomarkers were confirmed to be highly correlated with age (R(2) > 0.7). The growth plates of the lumbar vertebra and the femur began to close at 21 and 25 months of age, respectively, and closed completely at 42 months of age. Bone length increased rapidly before growth plate closure, and reached a peak at 21 and 28 months of age in the lumbar vertebra and the femur, respectively. The levels of BMC and BMD increased rapidly before growth plate closure, and continued to increase slowly until 76 months of age. A high negative correlation (-0.855 < r < -0.711, p<0.001) was confirmed between the bone biomarkers and the bone measurement data. These results indicate that the bone turnover velocity is consistent with the bone growth velocity in female G?ttingen minipigs.     

天津蓟州区桃花园墓地明清时期缠足女性的足骨形变

本文通过量化方法,对桃花园墓地明清时期101例女性足骨形变方式、程度、对称性等进行了系统分析。研究结果表明,双侧足骨形变总体上是对称的。缠足对跗骨的影响主要在于整体尺寸缩小和关节面改变。第1跖骨除整体尺寸缩小外,还存在诸多明显的骨体形态改变;第2、3跖骨头部和底部尺寸缩小,但形变不大。第3至第5近节趾骨骨体长度和高度的侧别差异明显,特别是第3近节趾骨双侧整体不对称。该群体至少在18岁时已经缠足,25岁以后足骨已发生形变,35岁之后形变较明显。部分个体足骨形变程度较轻,其生前可能仅束足纤直,未经裹弯。足骨形变程度与陪葬品多寡并无相关性,其形变差异很可能与身体疾病、劳作需要、缠足方法或缠足观念差异有关。     

Osteoprotegerin and bone density

Aim of study was determine if a correlation exists between bone mass density and concentration of osteoprotegerin. We examined the group of 199 patients of mean age of 63 years. Of the group under study, 31 patients had normal bone density (T score > -1 and < 1) and 168 probands had osteopenia or osteoporosis (T < -1). Persons with normal BMD values had median values of OPG 60.8 ng/l, while patients with reduced bone density had median values of 73 ng/l OPG. Cut-off for reduction of bone density was 128 ng/l OPG. We demonstrated that OPG concentrations vary inversely with bone density values (correlation coefficient -0.31). These results suggest that determination of OPG could allow discrimination of individuals with normal bone density and those with reduced bone density.     

Growth and bone maturation in children from two regions of the F.R.G. differing in the degree of air pollution: results of the 1974 and 1984 surveys

Growth and bone maturation criteria were used in this collaborative study to assess the potential health risk posed by excessive air pollutant emission. The study consisted of two surveys carried out 10 years apart. During this decade, a substantial emission reduction through the effective control efforts was achieved in the index area, but not so in the reference area where the situation remained virtually unchanged during this period. In terms of body height and height-weight proportionality, no significant differences were found between areas and years of investigation. In contrast, the bone age retardation encountered in the children from the polluted area was statistically significant, both at 1974 and 1984 surveys, despite the appreciable improvement in this developmental criterion for boys in 1984. This was true for both group mean values and the percentages of individuals exhibiting the bone maturation delay greater than 10 months.