Male rodent model of age-related bone loss in men

Osteoporosis is a common occurrence in aging men. There is currently no appropriate animal model for studying age-related bone loss in men. To determine whether male Sprague-Dawley (SD) rats experience bone loss with aging and whether this rodent model is appropriate for studying age-related bone loss in men, SD rats aged 1-27 months were examined at the L-4 vertebra, the left femoral neck, and the left proximal tibia using peripheral quantitative computed tomography (pQCT) densitometry. In the L-4 vertebra of the male SD rats, cortical bone mineral content (BMC), cortical bone mineral density (BMD), and cortical bone thickness (Ct.Th) increased to a maximum at about 4 months of age and then plateaued. Vertebral cortical BMC began to decrease after about 13 months and vertebral Ct.Th began to decrease after about 9 months. By 27 months of age, vertebral cortical BMC decreased by 26.1% (p < 0.0001) and vertebral Ct.Th decreased by 31% (p < 0.0001). Vertebral cancellous BMC and vertebral cancellous BMD increased to a maximum at about 3 months of age and then declined progressively with aging after a short plateau. From 3 to 27 months of age, vertebral cancellous BMC and vertebral cancellous BMD had decreased linearly by 35.4% (p < 0.0001) and 49.4% (p < 0.0001), respectively. Both vertebral periosteal and vertebral endocortical perimeters of the L-4 vertebra of the rats increased with aging. From 9 to 27 months of age, the percent increase of vertebral endocortical perimeter (19.8%, p < 0.0001) was higher than that of vertebral periosteal perimeter (7.4%, p < 0.0001). This process was associated with a decrease with aging in vertebral Ct.Th. In addition, cancellous bone in the femoral neck and the proximal tibia began to be lost at 9 months of age and, by 27 months of age, cancellous BMC and cancellous BMD decreased by 59.7% (p < 0.0001) and 58.4% (p < 0.0001), respectively, in the femoral neck and by 72.2% (p < 0.0001) and 71.4% (p < 0.0001), respectively, in the proximal tibia. To gain further insight into the effects of aging on cancellous bone in the L-4 vertebra, histomorphometry was done on the L-4 vertebral body of animals aged 3, 6, 9, 18, and 24 months after pQCT densitometry. From 3 months of age and thereafter, cancellous bone volume (BV/TV) decreased progressively and, by 24 months, there was a decrease of 35.7% (p < 0.0001). In the L-4 vertebra, single- and double-labeled surfaces, mineral apposition rate (MAR), and bone formation rate (BFR/BS) decreased with aging. In conclusion, age-related bone loss in male SD rats started mostly from 9 months of age when bone growth had been completed. Aging male SD rats experience bone loss comparable to that seen in men. Thus, male SD rats represent an appropriate animal model of age-related bone loss in men. We recommend using male SD rats that are 9 months old as the starting age for age-related bone loss. We also suggest using the L-4 vertebra and femoral neck as the clinically relevant bone sites for determining the cause of the loss of bone, and how and whether therapeutic agents could modulate age-related bone loss in men.     

Rodent Model for Investigating the Effects of Estrogen on Bone and Muscle Relationship During Growth

It has been reported that in humans from about 11-12 years of age, bone mass begins to increase faster in girls than in boys with the same muscle mass, and by 14-15 years of age, bone mass per unit mass of muscle was found to be significantly higher in girls than in boys. Because around 15 years is the beginning of reproductive age in women, it was suggested that estrogen was involved in the higher bone mass in women during puberty. The present study was undertaken to determine if bone mass per unit muscle mass is higher in female than in male Sprague Dawley (SD) rats during growth, as has been reported in humans during growth and consequently, whether these SD rats are suitable for studying the musculoskeletal effects of estrogen, as may occur in humans during growth. L-4 vertebra of female and male SD rats aged 1-6 months were studied using peripheral quantitative computed tomography (pQCT). Muscle cross-sectional area was measured as a surrogate for muscle mass and bone mineral content (BMC) was measured as a surrogate for bone mass. From 1 to 6 months of age, total BMC, cortical BMC, and cancellous BMC increased faster in females than in males with similar muscle area, and at 3 and 6 months of age, the above vertebral indices of bone mass were significantly higher in female than in male rats. Since one of the main differences between female and male rats is the level of serum estrogen, the higher bone mass per unit muscle area seen at the L-4 vertebra in these female SD rats is similar to what has been reported in humans during puberty when serum estrogen level is high in females. The findings from this study indicate that female and male SD rats aged 1-6 months can be used as appropriate model for studying the effects of serum estrogen on the skeletal response of voluntary muscle forces, as has been reported in humans during growth.     

Quantification of bone mineral contents using dual photon absorptiometry in a normal Japanese population — total body bone mineral

We established reference values for total body bone mineral of normal Japanese subjects utilizing dual photon absorptiometry. The index of measurement, total body bone mineral content (TBBM) divided by lean body mass (LBM), might be suitable for the evaluation of total body bone mineral. TBBM/LBM did not correlate with age in male subjects; however, reduced bone mineral was noted in female subjects after fifth decade. The rate of change in bone after the fifth decade was 0.82% per year. The bone mineral density (BMD) of each region including total body also showed a significant decrease with aging in women after the age of 40. Again no significant age-related changes were obtained in male BMD of any region (head, trunk, pelvis, legs, arms). The annual loss in women after the bone loss began was 0.72% in total body BMD. The rate of BMD change in each region of bone after 40 years of age ranged from 0.91% (trunk) to 0.51% (arms) per year. The bone mineral content (BMC) in “trunk” portion of TBBM decreased significantly with aging, while BMC of other portions did not show a significant age-related change. These results differ slightly from results which we have already reported for lumbar spine BMD, in which case average annual rates of bone loss once begun, were 0.32% for male and 0.97% for female.     

Effects of cerivastatin and parathyroid hormone on the lumbar vertebra of aging male Sprague-Dawley rats

Both men and women lose bone at a late age (aging bone loss). The aim of this study was to determine whether cerivastatin and parathyroid hormone (PTH) can prevent aging bone loss in men. Bone loss in aged male Sprague-Dawley (SD) rats was used as a model for age-related bone loss in men. Nine-month-old male SD rats were divided into six groups: (1) baseline controls (killed at the beginning of the study); (2) age-matched controls; (3) parathyroid hormone (PTH; 80 microg/kg body weight per day for 5 days/week) treated; (4) low-dose cerivastatin (0.2 mg/kg body weight per day) treated; and (5) medium-dose cerivastatin (0.4 mg/kg body weight per day) treated; and (6) high-dose cerivastatin (0.8 mg/kg body weight per day) treated. Groups 2-6 were treated for 23 weeks between the ages of 9 and 15 months and killed at the end of 23 weeks. The fourth lumbar vertebra was analyzed using peripheral quantitative computed tomography (pQCT). It is shown that age-matched controls had decreased cancellous bone mineral content (Cn. BMC) by 19% (p < 0.05) and cancellous bone mineral density Cn. BMD) by 22% (p < 0.01) when compared with baseline controls. All three doses of cerivastatin resulted in lower Cn. BMC and Cn. BMD when compared with age-matched controls, but this decrease was not statistically significant. In the PTH-treated group, Cn. BMC increased by 5% (p < 0.0001) and Cn. BMD increased by 37% (p < 0.0001) when compared with age-matched controls. In age-matched controls, cortical bone mineral content (Ct. BMC) and cortical bone mineral density (Ct. BMD) decreased slightly, but not significantly, when compared with baseline controls. Ct. BMD did not change significantly at any of the three doses in the cerivastatin-treated groups. In the PTH-treated group, Ct. BMC increased by 23% (p < 0.0001) when compared with age-matched controls. We confirmed that male SD rats lose bone with aging in the lumbar vertebra, and it is concluded that cerivastatin, at all doses administered, did not prevent this age-related bone loss. In contrast, PTH prevented age-related bone loss in the vertebra of male SD rats.     

Decreased bone anabolic effect of basic fibroblast growth factor at fatty marrow sites in ovariectomized rats

The purpose of the study was to compare the bone anabolic effects of basic fibroblast growth factor (bFGF) at hematopoietic (red) and fatty (yellow) marrow sites in ovariectomized (ovx) rats. Female Sprague Dawley rats were subjected to ovariectomy or sham surgery at 3 months of age and maintained untreated for 2 months after surgery. Three groups of ovx rats were then injected intravenously with bFGF for 14 days at a dose of 200 microg/kg body weight. One group of bFGF-treated OVX rats was killed at the end of the treatment period, whereas the other two groups were killed at 7 or 14 days after withdrawal of bFGF treatment. Another group of ovx rats and a group of sham-operated control rats were treated intravenously with vehicle alone for 14 days. The proximal tibia and first lumbar vertebra, bone sites with hematopoietic marrow, as well as the distal tibia and caudal vertebra, bone sites with primarily fatty marrow, were processed undecalcified for quantitative bone histomorphometry. At the hematopoietic marrow sites, bFGF treatment induced a marked accumulation of osteoid, which calcified during the withdrawal period to result in a significant increase in cancellous bone volume. Osteoblast and osteoid surfaces were increased by at least a factor of 10 at these sites in bFGF-treated ovx rats before declining rapidly during the withdrawal period. In contrast, osteoid volume was negligible in the fatty marrow sites of bFGF-treated ovx rats. Although these animals exhibited a nonsignificant trend for increased cancellous bone volume in the fatty distal tibia during the withdrawal period, no such trend was observed in the fatty caudal vertebra. Indices of bone formation (osteoblast and osteoid surfaces) were significantly increased by bFGF treatment in the fatty distal tibia, which retained some small pockets of hematopoietic cells, but not to the same great extent as in the skeletal sites with hematopoietic marrow. Furthermore, not even a trend for increased osteoblast and osteoid surfaces was observed in the fatty caudal vertebra of bFGF-treated ovx rats. These findings indicate that bFGF is a strong bone anabolic agent at skeletal sites with hematopoietic marrow, but the stimulatory effects of the growth factor on bone formation are greatly attenuated at fatty marrow sites.     

Nondestructive measurement of bone mineral in femurs from ovariectomized rats

Summary One hundred ninety-eight rats were ovariectomized (OX) or sham-ovariectomized (shOX) at 100 days of age. Groups were killed at 35, 70, 100, 125, 180, 270, 360, and 540 days postsurgery. Bone mineral content (BMC) of the right femur was assayed on a dual photon absorptiometer (DPA) optimized for human spine and whole body measurements. Three regions were studied: the distal measuring 0.8 cm, the proximal measuring 0.88 cm, and the diaphysis, the remainder. The DPA technique accurately showed the ash content (r=0.96), with a precision error of 3–5%. Whole femoral BMC was 4.3–11.1% lower in OX than shOX rats, with significant differences from 35–180 days. By 35 days, distal femoral BMC declined 6% in OX rats and rose 12% in shOX rats. Distal femoral BMC was 11.3–17.5% lower in OX than shOX rats, with significant differences at all times except 540 days. Femoral diaphyseal BMC of OX and shOX rats did not differ at any time. The relative distal femoral osteopenia which appeared by 35 days in OX rats did not worsen during the next 17 months. A DPA suited for human BMC studies is also accurate for BMC determination in bones with 250–500 mg of mineral It is less precise for this purpose than dedicated instruments using single photon absorptiometry. However, enough precision exists to monitor the development of relative osteopenia in OX rats. Osteopenia in OX rats is confined to a region containing appreciable cancellous bone. Its self-limiting nature suggests the existence of an estrogen-dependent quantum of cancellous bone in female rats. The adult rat model is accurate for cancellous bone of the adult human, but inaccuare for cortical bone.     

Bone mineral content in the senescent rat femur: an assessment using single photon absorptiometry

The single photon absorptiometry technique was evaluated for measuring bone mineral content (BMC) of the excised femurs of the rat, and the system was used to examine the changes in cortical and trabecular bone from young adult (6 mo), mature adult (12 mo), and senescent (24 mo) male and female animals. BMC of the femur midshaft, representing cortical bone, apparently increased progressively with advancing age. The width of the femur at the scan site also increased with age. Normalizing the midshaft BMC by width partially compensated for the age-associated increase. However, when bone mineral values were normalized by the cortical area at the scan site, to take into account the geometric differences in the femurs of different aged animals, maximum bone densities were found in the mature adult and these values decreased slightly in the femurs from senescent rats. In contrast, the BMC of the femur distal metaphysis, representing trabecular bone, decreased markedly in the aged rat. The loss of trabecular bone was also evident from morphological examination of the distal metaphysis. These findings indicated that bone mineral loss with age was site specific in the rat femur. These studies provided additional evidence that the rat might serve as a useful animal model for specific experiments related to the pathogenesis of age-associated osteopenia.     

Multigenerational exposure to genistein does not increase bone mineral density in rats

Genistein has been shown to prevent bone loss in ovariectomized adult rats. However, the effects of genistein on bone in developing and reproductively-intact rats have not been examined. A large multigenerational experiment involved feeding 0, 5, 100, or 500 ppm genistein in the diet to intact male and female rats from conception until either weaning, postnatal day 140, or continuously for 2 years. Vertebrae (lumbar and caudal) were collected from these animals at necropsy at 2 years of age and subjected to dual-energy x-ray absorptiometry (DXA) scanning to measure bone mineral density (BMD), bone mineral content (BMC), and bone area. Femurs were collected, and length, cross-sectional area, and cortical bone area were measured directly. Serum was collected for measurement of pyridinoline (PYD) and alkaline phosphatase (ALP). BMD was not affected by genistein in any phase of the experiment. In female rats treated continuously with genistein, BMC and bone area were reduced in the 500 ppm group compared to the 5 ppm group in the lumbar vertebrae, and in all treatment groups compared to control in the caudal vertebrae. In both males and females treated continuously, the cross-sectional area of the femur was reduced in rats treated with 500 ppm compared to those treated with 5 ppm. In female rats treated continuously, PYD was higher in the 100 and 500 ppm groups than in the 0 and 5 ppm groups. In conclusion, the effects of genistein on reproductively-intact rats were not dramatic. High dose of genistein throughout the lifespan resulted in decreased bone size, which may reduce the force required to break the bone.     

Bone mineral density of proximal femur and spine in Korean children between 2 and 18 years of age

Ethnic factors affect bone mass acquisition during childhood. The aim of our study was to establish normative data for bone mineral content (BMC) and bone mineral density (BMD) in healthy Korean children and adolescents, using 446 lumbar spine scans (224 males and 222 females) and 364 proximal femur scans (181 males and 183 females) of healthy children between ages 2 and 18 years measured by dual-energy X-ray absorptiometry using Hologic QDR Discovery A 2004. There was an increase in both BMC and BMD during early childhood, acceleration during the adolescence spurt, and a slower increase later. Until 11 years of age, both male and female BMC and BMD were not statistically different. There was a rapid increase in both BMC and BMD in females earlier than in males, and later males caught up with the females and overshot the female values. When compared with Canadian children, BMD and BMC of total proximal femur was found to be more and BMD and BMC of total lumbar spine to be less at some ages. Tanner's stage was significantly associated with BMD and BMC of spine and proximal femur in males and BMC of spine in females in the first three Tanner's stages. Height, body weight, fat content, and body mass index influenced BMC and BMD at different sites by variable amount. Hence, the values presented in this study should be used as reference values in Korean children and adolescents.     

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

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

Intermittent administration of bovine PTH-(1-34) increases serum 1,25-dihydroxyvitamin D concentrations and spinal bone density in senile (23 month) rats.

We examined the effect of intermittent administration of bovine parathyroid hormone (1-34) (bPTH) on spinal bone mineral content (BMC) and bone mineral density (BMD), serum 1,25-dihydroxyvitamin D concentrations, and serum markers of osteoblast function in senile male and female rats (23 and 24 months of age, respectively). Sexually mature young (3 month) male rats were similarly treated for comparison. bPTH administration increased serum osteocalcin concentrations without changing serum inorganic phosphate or calcium concentrations in either group of old animals. In young animals, PTH administration increased the serum calcium and inorganic phosphate concentrations significantly (p less than 0.05), although values remained within the normal range. In the vehicle-treated male rats, serum 1,25-dihydroxyvitamin D concentrations were lower in the senile than in the young animals (18 +/- 5 versus 47 +/- 6 pg/ml, p less than 0.05). PTH administration resulted in significantly increased serum 1,25-dihydroxyvitamin D concentrations in the senile and young male animals (both, p less than 0.05) and the final mean serum 1,25-dihydroxyvitamin D concentrations were not statistically different (68 +/- 9 versus 85 +/- 6 pg/ml respectively; p = NS). Serum 1,25-dihydroxyvitamin D concentrations were significantly (p less than 0.05) higher in the PTH-treated senile female rats than the sex-matched, vehicle-treated controls. The pretreatment spinal BMC and BMD as assessed by dual-energy x-ray absorptiometry (DEXA) were significantly higher in the senile male animals than in the young animals. Spinal BMC and BMD decreased in the vehicle-treated senile male rats (p less than 0.05) over the 3 weeks of the study despite a gain in weight.(ABSTRACT TRUNCATED AT 250 WORDS)     

A nonhuman primate model of age-related bone loss: a longitudinal study in male and premenopausal female rhesus monkeys

Aging is associated with gradual bone loss in men and premenopausal women, with an accelerated rate of loss after menopause in women. Although many studies have investigated bone loss due to surgically induced estrogen depletion, little is known regarding normal age-related changes in bone mass in animal models. We used dual-energy X-ray absorptiometry (DXA) to measure bone mineral density (BMD), bone mineral content (BMC), and projected area (PA) at four skeletal sites over 4 years in 20 premenopausal female (8-23 years) and 29 male (8-27 years) rhesus monkeys (Macaca mulatta). Forearm BMD declined with age in both male and female monkeys. Lean mass was positively associated with BMD at all sites in males and with the distal radius in females. Serum osteocalcin declined and urinary cross-links increased with age in males but not females. Serum 25-hydroxyvitamin D concentrations decreased with age in females, and a similar trend was observed in males. In conclusion, an age-related decline in forearm BMD was observed in male and female rhesus monkeys. Total body BMC declined over time in older females, with a similar trend in males. Changes in markers of bone turnover with age were also observed in male monkeys. The results of this longitudinal study suggest that the rhesus monkey is a potential model for age-related changes in the human skeleton.     

Bone Densitometry in Canadian Children 8–17 Years of Age

Normative bone mineral density (BMD) and bone mineral content (BMC) values for the total body (TB), proximal femur (PF), and antero-posterior lumbar spine (LS) were obtained from a large cross-sectional sample of children and adolescents who were 8–17 years of age. There were 977 scans for the TB, 892 for the PF, and 666 for the LS; bone mineral values were obtained using a HOLOGIC QDR 2000 in array mode. Data are presented for the subregions of the PF (femoral neck, trochanter, intertrochanter, and the total region) and for the LS (L1–L4 and L3). Female and male values for the FN, LS (L1–L4), and the TB were compared across age groups using a two-way ANOVA. In addition, we compared the 17-year-old female values to a separate sample of young adult women (age 21). At all these sites, BMC and BMD increased significantly with age. There was no gender difference in TB BMC until age 14 or in TB BMD until age 16, when male values were significantly greater. Females had significantly greater LS BMC at ages 12 and 13, but by age 17 the male values were significantly greater. Females had significantly greater LS BMD across all age groups, however. Males had significantly greater FN BMC and BMD across all age groups. There were no significant differences in BMC or BMD at any sites between the 17- and 21-year-old women. Received: 29 September 1995 / Accepted: 1 April 1996     

Histologic evidence for osteopenia and increased bone turnover in ovariectomized rats

Bone histomorphometry was performed in the proximal tibia and lumbar vertebra of female Sprague-Dawley rats subjected to either bilateral ovariectomy or sham surgery. Ovariectomized rats killed 10 weeks after surgery were characterized by osteopenia and histomorphometric indices of increased bone turnover at both skeletal sites. Osteoclast surface and number as well as osteoblast surface and number were significantly increased in ovariectomized rats. Tetracycline-based data were consistent with accelerated bone formation in response to ovariectomy. Active formation surface (double-labeled surface), calcification rate, and bone formation rate (tissue level, total surface referent) were all significantly elevated in the proximal tibia of ovariectomized rats. Ovariectomy also increased active formation surface and bone formation rate in the lumbar vertebra, but the vertebral calcification rate was nearly identical in control and ovariectomized rats. Osteopenia and dynamic tetracycline-based estimates of increased bone turnover in ovariectomized animals were more pronounced in the proximal tibia relative to the lumbar vertebra. Longitudinal bone growth in the proximal tibia and mineralization lag time at the tibial cortical endosteal surface were not affected by ovariectomy. These histomorphometric data indicate that ovariectomy induces osteopenia and accelerated skeletal metabolism in rats.     

中等强度跑台运动对去卵巢大鼠后肢骨骨矿物含量和骨密度的双重调节作用

目的 观察中等强度跑台运动对去卵巢大鼠后肢骨骨矿物含量(BMC)和骨密度(BMD)的影响.方法 将60只3月龄未经产雌性SD大鼠按体重随机分为假手术、去卵巢静止、去卵巢运动Ⅰ、去卵巢运动Ⅱ、去卵巢运动Ⅲ和去卵巢运动Ⅳ 6个组.各运动组经1周的跑台适应训练后,按实验设计分别进行为期14周的正式跑台训练.实验结束时,腹主动脉取血处死大鼠,双能χ-射线骨密度仪检测右侧游离股骨和胫骨的BMC和BMD.结果 ①与假手术组相比,去卵巢静止组股骨近端和远端以及胫骨近端BMC和BMD显著下降,但股骨中段以及胫骨中段和远端BMC和BMD无显著变化.②与去卵巢静止组相比,去卵巢运动Ⅰ组股骨近端和远端BMC显著增加,股骨中段以及胫骨3个部位BMC均无显著变化;去卵巢运动Ⅱ组和Ⅲ组股骨和胫骨3个部位BMC 均无显著变化;去卵巢运动Ⅳ组股骨3个部位BMC均无显著变化,而胫骨3个部位BMC均显著下降.③与去卵巢静止组相比,去卵巢运动Ⅰ组股骨近端和远端以及胫骨近端BMD 显著增加, 而股骨中段和胫骨中段和远端BMD无显著变化;去卵巢运动Ⅱ组和Ⅲ组股骨和胫骨任何部位BMD均没有显著变化;去卵巢运动Ⅳ组股骨3个部位BMD无显著变化,而胫骨3个部位BMD却显著下降.结论 较低中等强度跑台运动能减缓去卵巢大鼠股骨近端和远端骨矿物含量和骨密度的下降;而较高中等强度跑台运动却能加速去卵巢大鼠胫骨近端骨矿物含量和骨密度的下降.     

Effects of long-term calcium intake on body weight, body fat and bone in growing rats

Increased calcium intake may reduce body weight and fat in non-growing individuals. This study explored the long-term effects of high versus low calcium intake on body weight, body fat, BMC, BMD and bone size in growing male and female rats. Ninety male and 90 female Sprague-Dawley rats were randomly assigned either to a high calcium (1%) or low calcium (0.25%) diet from age 3 weeks until 40 weeks. Half of the animals were fed ad libitum, and half of the animals were on an adjusted feeding schedule (the food intake of the low calcium animals was reduced to maintain equal body weight with high calcium animals of the same gender). DXA and radiographic measurements (femur and skull length and width) were collected at the age of 4, 13 and 34 weeks. Growing male rats fed the low calcium diet ad libitum gained more weight and more fat than rats on a high calcium diet. When food intake was controlled, male rats on the low calcium diet still had a greater fat mass (despite their similar body weight) and smaller skeletal measurements than the high calcium animals. Growing female rats initially responded like the males: when fed ad libitum low calcium animals had an increased body weight and fat mass; when food intake was controlled the low calcium animals had a greater fat mass and smaller skeletal measurements. However, these differences were found at 13 weeks and not at 34 weeks, suggesting a transient effect with no long-term differences between high and low calcium intake in the growing female rats.     

Mineral content of upper tibia assessed by dual photon densitometry

Bone mineral content (BMC, g/cm) and bone mineral density (BMD, g/cm²) of the proximal tibia were determined by dual photon absorptiometry (DPA). Measurements just distal to the subchondral plates of the tibia condyles, where the bone structure is predominantly trabecular, proved to give the most consistent results. The precision of BMC measurements in this region, expressed as the coefficient of variation, was 1.1 per cent and of BMD measurements 2.5 per cent.

In a cross-sectional study on 63 normal women and men, BMC and BMD showed a decrease with age at a rate of about 8 and 9 per cent per decade, respectively, in women, but not in men. In normal women, BMC of proximal tibia was correlated with BMC of lumbar spine, femoral neck, and femoral shaft, as well as with body weight and height. DPA may be useful in the study of bone reactions, such as in patients undergoing arthroplasty of the knee.     

Mineral content of upper tibia assessed by dual photon densitometry

Bone mineral content (BMC, g/cm) and bone mineral density (BMD, g/cm2) of the proximal tibia were determined by dual photon absorptiometry (DPA). Measurements just distal to the subchondral plates of the tibia condyles, where the bone structure is predominantly trabecular, proved to give the most consistent results. The precision of BMC measurements in this region, expressed as the coefficient of variation, was 1.1 per cent and of BMD measurements 2.5 per cent. In a cross-sectional study on 63 normal women and men, BMC and BMD showed a decrease with age at a rate of about 8 and 9 per cent per decade, respectively, in women, but not in men. In normal women, BMC of proximal tibia was correlated with BMC of lumbar spine, femoral neck, and femoral shaft, as well as with body weight and height. DPA may be useful in the study of bone reactions, such as in patients undergoing arthroplasty of the knee.     

Dual photon absorptiometry of the proximal tibia

Summary Bone mineral content (BMC) and bone mineral density (BMD) of the proximal tibia were determined by dual photon absorptiometry on 44 women, aged 23–87 years. The area of the tibia measured was a 2.01 cm region immediately distal to the medial and lateral tuberosities. Values of BMC ranged between 5.09 and 14.57 g and BMD between 0.380 and 1.180 g/cm². Both tibial BMC and BMD declined with age and tibial BMD was significantly correlated with lumbar spine (r=0.70), femoral neck (r=0.73), and femoral trochanter (r=0.74). However, the large standard errors of estimate (SEE) (0.08–0.14 g/cm²) do not allow for reliable prediction in an individual of other skeletal sites by the tibia. Repeated measurements demonstrated that dual photon absorptiometry of the proximal tibia is a reliable measurement and may be a useful tool in the monitoring of therapeutic or intervention modalities in those individuals with skeletal diseases in whom measurement of the lumbar spine or proximal femur may not be possible.     

Effect of ovariectomy and prednisolone on bone mineral content in rats: Evaluation by single photon absorptiometry and radiogrammetry

Summary The effects of ovariectomy and prednisolone were studied for 9 months in 3-month-old rats on a moderately low calcium diet. Measurements were made by single photon absorptiometry of the femur at cortical and trabecular bone sites. Radiogrammetry was performed at the midshaft of the femur. During growth, body weight, bone size, and bone mineral content (BMC) increased in male rats more than in females. After ovariectomy, body weight increase was more pronounced, but bone mineral increase was lower than in controls. At the distal end of the femur, bone mineral density decreased after 3 months, and at the midshaft of the femur, medullary width increased significantly from 6 months on. Prednisolone in a dose of 0.5 mg/kg/day did not influence BMC. However, prednisolone treatment after ovariectomy induced a more pronounced effect on bone than ovariectomy alone. BMC increase was lower than in ovariectomy, and bone mineral density decreased significantly, especially at the distal end of the femur. After correction for differences in body weight, globally the same results were found. We conclude that (1) the combination of single photon absorptiometry and radiogrammetry allows the evaluation of growth and the effect of ovariectomy and prednisolone treatment in rats; (2) ovariectomy results in bone loss first at the distal end and later in the midshaft of the femur; (3) prednisolone in a dose of 0.5 mg/kg/day alone did not affect bone mass; and (4) prednisolone profoundly enhanced the effects of ovariectomy.