scispace - formally typeset
Search or ask a question

Showing papers in "Calcified Tissue International in 1995"


Journal ArticleDOI
TL;DR: Mechanotransduction plays a crucial role in the physiology of many tissues including bone and some hormones may interact with local mechanical signals to change the sensitivity of the sensor or effector cells to mechanical load.
Abstract: Mechanotransduction plays a crucial role in the physiology of many tissues including bone. Mechanical loading can inhibit bone resorption and increase bone formation in vivo. In bone, the process of mechanotransduction can be divided into four distinct steps: (1) mechanocoupling, (2) biochemical coupling, (3) transmission of signal, and (4) effector cell response. In mechanocoupling, mechanical loads in vivo cause deformations in bone that stretch bone cells within and lining the bone matrix and create fluid movement within the canaliculae of bone. Dynamic loading, which is associated with extracellular fluid flow and the creation of streaming potentials within bone, is most effective for stimulating new bone formation in vivo. Bone cells in vitro are stimulated to produce second messengers when exposed to fluid flow or mechanical stretch. In biochemical coupling, the possible mechanisms for the coupling of cell-level mechanical signals into intracellular biochemical signals include force transduction through the integrin-cytoskeleton-nuclear matrix structure, stretch-activated cation channels within the cell membrane, G protein-dependent pathways, and linkage between the cytoskeleton and the phospholipase C or phospholipase A pathways. The tight interaction of each of these pathways would suggest that the entire cell is a mechanosensor and there are many different pathways available for the transduction of a mechanical signal. In the transmission of signal, osteoblasts, osteocytes, and bone lining cells may act as sensors of mechanical signals and may communicate the signal through cell processes connected by gap junctions. These cells also produce paracrine factors that may signal osteoprogenitors to differentiate into osteoblasts and attach to the bone surface. Insulin-like growth factors and prostaglandins are possible candidates for intermediaries in signal transduction. In the effector cell response, the effects of mechanical loading are dependent upon the magnitude, duration, and rate of the applied load. Longer duration, lower amplitude loading has the same effect on bone formation as loads with short duration and high amplitude. Loading must be cyclic to stimulate new bone formation. Aging greatly reduces the osteogenic effects of mechanical loading in vivo. Also, some hormones may interact with local mechanical signals to change the sensitivity of the sensor or effector cells to mechanical load.

962 citations


Journal ArticleDOI
TL;DR: These studies are consistent with a deficit of osteoprogenitor cells in the bone marrow site as a contributing, perhaps correctable factor in the decline in bone repair and bone mass with age.
Abstract: Aging bone shows a progressive decline in mass and strength. Previous studies have suggested that bone marrow stem cells are reduced with aging and that this could be responsible, in part, for age-associated bone deficits. We measured the number of osteoprogenitor cells present in the bone marrow from adult and aged rats as well as their ability to differentiate in vitro and to form bone in vivo. We found that the number of adherent colony-forming cells was significantly lower (65%) in marrow cells isolated from aged compared with adult rats. Furthermore, 88% of the colonies obtained from aged rats were alkaline phosphatase (AP) positive, whereas virtually all the colonies from adult rats were positive. The addition of dexamethasone to the culture medium decreased the proliferation of the adherent cells and reduced the number of colonies obtained from both adult and aged bone marrow, all of which were AP positive. No significant differences were found in the expression of certain major bone cell marker genes as a function of donor age. However, dexamethasone treatment increased expression of osteopontin (OP) by fivefold. Adult stromal cells not treated with dexamethasone and implanted subcutaneously in recipient rats exhibited about 10-fold greater formation of bone compared with cells from aged rats. In contrast, dexamethasone-treated cells exhibited high levels of bone formation, irregardless of donor age or the age of the recipient into which the cells were grafted. These studies are consistent with a deficit of osteoprogenitor cells in the bone marrow site as a contributing, perhaps correctable factor in the decline in bone repair and bone mass with age.

342 citations


Journal ArticleDOI
TL;DR: Preliminary results demonstrate that estrogens may protect bone in male subjects also and may merit further investigations on larger groups of patients.
Abstract: Bone mineral density (BMD) and bone mineral content (BMC) were measured in the femoral neck area, trochanteric area and Wards triangle, and in the distal radius of the left forearm before and after 1 year of endocrine treatment in 27 patients with prostatic cancer. Eleven of the patients were treated with orchidectomy and 16 with combined oral and intramuscular estrogens. The patients were free from metastases during the entire observation period. In the orchidectomized patients, BMD and BMC of the distal radius decreased significantly following treatment, whereas no changes were observed in the estrogen-treated patients. These preliminary results demonstrate that estrogens may protect bone in male subjects also and may merit further investigations on larger groups of patients.

184 citations


Journal ArticleDOI
TL;DR: It appears that both femoral and calcaneal bone mineral properties may be useful for identifying those persons at greatest risk for hip fracture.
Abstract: We assessed the bone mineral density (BMD) of 16 matched sets of cadaveric proximal femurs and feet using dual-energy x-ray absorptiometry (DXA). We also estimated the femoral neck length from the DXA scans. Quantitative ultrasound densitometry was used to measure the velocity of sound and broadband ultrasound attenuation (BUA) in the calcaneus of each foot. The proximal femurs were then tested to failure in a loading configuration designed to simulate a fall with impact to the greater trochanter. Femoral neck BMD and trochanteric BMD were strongly associated with the femoral failure load (r2=0.79 and 0.81, respectively; P<0.001), whereas femoral neck length was modestly correlated with femoral failure load (r2=0.27, P=0.04). Calcaneal BMD (r2=0.63, P<0.001) and BUA (r2=0.51, P=0.002) were also significantly associated with femoral failure load. Given the small sample size, we were unable to detect differences in the strength of the correlations between the independent parameters and femoral failure load. Using linear multiple regression analyses, the strongest predictor of femoral failure load was a combination of femoral neck BMD and femoral neck length (R2=0.85, P<0.001). Thus, it appears that both femoral and calcaneal bone mineral properties may be useful for identifying those persons at greatest risk for hip fracture.

172 citations


Journal ArticleDOI
TL;DR: Results indicate that the 17 kDa antigen (ovocleidin 17, OC-17) is secreted during shell formation and becomes incorporated into this structure, and may play a role in the crystallization process and influence the properties of the resulting eggshell.
Abstract: The protein components of biomineralized structures (matrix proteins) are believed to modulate crystal nucleation and growth, and theraby influence the shape and strength of the final structure. The chicken eggshell contains a complex array of distinct matrix proteins. The most abundant of these was purified to homogeneity by a combination of anionic exchange and hydroxyapatite chromatographies. Antibodies to this protein were raised in rabbit, and utilized for Western blotting and immunohistochemistry. These studies indicated that the 17 kDa antigen (ovocleidin 17, OC-17) is found in the shell gland mucosa, and that only the tubular gland cells were positive. Immunohistochemistry with decalcified shell indicated that OC-17 is uniformly distributed throughout the shell matrix, but concentrated in the mammillary bodies. Our results indicate that this protein is secreted during shell formation and becomes incorporated into this structure. It may therefore play a role in the crystallization process and influence the properties of the resulting eggshell.

141 citations


Journal ArticleDOI
TL;DR: It is concluded that QCT and mL-DXA are superior to PA- DXA and L-DX a in detecting bone loss in patients with DJD and, for these patients, BMD assessment by QCT or mL-DJD may be advisable.
Abstract: We assessed the impact of various forms of spinal degenerative joint disease (DJD) on bone mineral density (BMD) measured by quantitative computed tomography (QCT) and dual X-ray absorptiometry (DXA) in a group of postmenopausal women. Lateral (T4-L4) and AP (L1-L4) spinal radiographs were reviewed for fracture and DJD in 209 women (mean age 62.6 +/- 6.7). The severity of DJD findings was graded as 0, 1, or 2 on the lumbar films, except for vertebral osteophytes which were graded from 0 to 3. Vertebral fractures were defined semiquantitatively as approximately 20% reduction in anterior, middle, or posterior vertebral height. BMD was measured in all subjects by QCT and DXA, including posteroanterior DXA (PA-DXA), lateral DXA (L-DXA) and midlateral DXA (mL-DXA). When BMD was measured by QCT and mL-DXA in the 168 women without fractures, no significant differences were found between women with and those without DJD. However, BMD by PA-DXA was significantly higher in women with DJD changes, particularly when osteophytes were present at the vertebral bodies or facet joints. BMD by L-DXA was less affected by DJD. For this measurement a significant increase in BMD was only noted in subjects with vertebral osteophytes. Multivariate analysis of variance (MANOVA) showed that BMD by QCT and mL-DXA was not affected by DJD. In contrast, for all women, BMD by PA- and L-DXA was affected more by DJD than by fracture status. Chi-square testing demonstrated no significant relationships between vertebral fractures and any of the DJD changes. We conclude that QCT and mL-DXA are superior to PA-DXA and L-DXA in detecting bone loss in patients with DJD. Thus, for these patients, BMD assessment by QCT or mL-DXA may be advisable.

137 citations


Journal ArticleDOI
TL;DR: In conclusion, ultrasound measurements of bone in children provide both good precision and discrimination of normals from osteopenic patients.
Abstract: Ultrasound bone measurement in healthy (n = 71) and osteopenic (n = 18) children aged 6 through 13 years of both sexes has been evaluated using the Achilles densitometer (Lunar Corporation). Measurements on the os calcis included speed of sound (SOS), broadband ultrasound attenuation (BUA), and a calculated "stiffness" index. The Achilles was adapted for children by a special positioning procedure that included the use of foot shims, and beam collimation on the receiving transducer. The precision of ultrasound results was comparable to that in adults (0.2% for SOS, 1.5% for BUA, and 1.8% for stiffness). SOS, BUA, and stiffness values increased with age in both sexes. Ultrasound measurements were correlated with bone mineral density (BMD in g/cm2) of the heel, AP spine (L2-L4), and total body by dual X-ray absorptiometry (DXA) densitometry (Lunar DPX-L). SOS, BUA, and stiffness measurements were significantly lower in osteopenic children (Z approximately -1.9 to -2.5) (P < 0.0001) than in normal age-matched controls. Total body BMD showed a higher Z-score than stiffness (-3.3 versus -2.5), but stiffness showed a greater percentage decrease (-30% versus -18%). In conclusion, ultrasound measurements of bone in children provide both good precision and discrimination of normals from osteopenic patients.

135 citations


Journal ArticleDOI
TL;DR: It is concluded that bone mineral properties measured at the lumbar spine provide a valid assessment of the compressive strength of both thoracic andlumbar vertebrae and may be used to derive an index for the prediction of thoracolumbar fractures to aid in the early intervention of vertebral fractures.
Abstract: Fractures of the thoracic spine account for a large portion of vertebral fractures in the elderly, yet noninvasive measurements of bone mineral properties are limited to the L2–L4 vertebral bodies. The purpose of this investigation was to determine whether bone mineral properties of the umbar spine correlate with the failure properties of thoracic ertebrae. Cadaveric lumbar segments were scanned using dual-energy x-ray absorptiometry (DXA) from both the latcrol and anteroposterior projections. Three-body segments L1–L3 and T10–T12 were then compressed to create crush tractures in the L2 and T11 vertebral bodies, and linear corelation analyses were performed to compare each DXA measure with the failure properties of L2 and T11. Lumbar BMD from the lateral view correlated significantly with T11 altimate load (r=0.94, P<0.001), as did lumbar BMD from the anteroposterior projection (r=0.83, P=0.001). Significant correlations were also found between both lumbar BMD and BMC and the stiffness and energy to failure of I'll. Furthermore, BMD and BMC measured at L2 correlated significantly with L2 ultimate load, stiffness, and energy to failure. We conclude that bone mineral properties measured at the lumbar spine provide a valid assessment of the compressive strength of both thoracic and lumbar vertebrae. Lumbar BMD may therefore be used to derive an index for the prediction of thoracolumbar fractures to aid in the early intervention of vertebral fractures.

134 citations


Journal ArticleDOI
TL;DR: Bone mineral content (BMC) at both spine and total body was significantly associated with VDR gene alleles, and a similar association was noted between allele and body size variables, particularly weight.
Abstract: We determined vitamin D receptor (VDR) gene alleles (based on the BsmI restriction site polymorphism), duodenal mucosal receptor density, bone mass at spine and total body, and body size in 32 healthy premenopausal females. While we found no relationship between allele and receptor density in duodenal mucosa, bone mineral content (BMC) at both spine and total body was significantly associated with VDR gene alleles. BMC was highest for the bb allele, lowest for BB, and intermediate for Bb. A similar association was noted between allele and body size variables, particularly weight. When BMC was adjusted for body weight, the association with VDR polymorphism disappeared. The VDR gene polymorphism may be affecting bone mass not through classical nutritional mechanisms (e.g., intestinal calcium absorption), but through an influence on body size.

130 citations


Journal ArticleDOI
TL;DR: The age at menarche may have a strong association with peak bone mass, as suggested by the positive correlation of early menarches with high BMD observed in this study.
Abstract: The study of background factors in individuals with high bone mineral density (BMD) may provide useful information in the prevention of osteoporosis. We investigated the relationship of reproductive factors to BMD. In 519 female volunteers (327 postmenopausal and 192 premenopausal women) ranging in age from 21 to 74 (mean 52.3 ±11.8) years, spinal BMD values were obtained using both quantitative computed tomography and dual x-ray absorptiometry. The z score was calculated from the mean BMD in each 5-year age group, and high BMD and low BMD was defined as BMD with z score >+1.5 and <-1.5, respectively. Normal BMD was defined as BMD within the range-1.0

130 citations


Journal ArticleDOI
TL;DR: Androgen receptors are present at low densities in osteoblasts as discussed by the authors, which may inhibit bone resorption indirectly, by an inhibition of the recruitment of osteoclast precursors from bone marrow, by decreased secretion of interleukin-6 and/or prostaglandin E2, and by an increased sensitivity of marrow cells or osteoblast-like cells for PTH.
Abstract: Androgen receptors are present at low densities in osteoblasts. Androgens are also metabolized in bone. (Non)aromatizable androgens probably induce proliferation of osteoblasts and differentiation. A direct effect of androgens on osteoclasts has not been demonstrated. Androgens may however inhibit bone resorption indirectly, by an inhibition of the recruitment of osteoclast precursors from bone marrow, by decreased secretion of interleukin-6 and/or prostaglandin E2, and/or by an increased sensitivity of marrow cells or osteoblasts for bone resorption stimulating factors such as PTH. The recent demonstration of androgen receptors in bone marrow stromal and osteoclast-like cells opens new perspectives in this respect. During puberty, androgens stimulate bone growth both directly and indirectly. Observations in androgen-resistant animals clearly demonstrated that the sexual dimorphism of bone depends on the presence of a functional androgen receptor. Optimal peak bone mass seems related to an appropriately timed androgen secretion. In adults, androgens are also involved in maintenance of the male skeleton. Androgen replacement may prevent further bone loss in hypogonadal men, however, it seems difficult to fully correct bone mass in these men.

Journal ArticleDOI
TL;DR: The results indicate that antiresorptive drugs may be of benefit in the high turnover osteoporosis of OLT recipients, and serum calcium, phosphorus, iPTH, 25OHD3, and 1,25(OH)2D3 were within normal range.
Abstract: Osteopenia is a major complication of orthotopic liver transplantation (OLT). However, no effective therapy for bone disease has been defined. We have studied vertebral bone mineral density (VMD) and fasting serum markers of bone formation [bone gla protein (BGP), procollagen I carboxyterminal peptide (PICP)] and metabolism (serum Ca, P, intact parathyroid hormone (iPTH), 25OHD3 and 1,25(OH)2D3) in 120 patents after OLT. VMD was measured by dual-energy X-ray absorptiometry (DXA) using a Hologic QDR 1000 densitometer on two occasions, 12 months apart. Patients with OLT had a VBD significantly lower compared with age- and sexed-matched Spanish controls (P<0.05). Prevalence of osteoporosis (Z score below-2 SD) was 35.8%. Serum BGP (8.6±0.7 ng/ml) and PICP (222.9±81.9 ng/dl) were higher than those of controls. However, serum calcium, phosphorus, iPTH, 25OHD3, and 1,25(OH)2D3 were within normal range. Patients with osteoporosis were randomly treated with 40 IU/day of calcitonin i.m. (Diatin, Ferrer Int. Laboratories) (n=17) or 400 mg p.o., 15 days every 3 months, of sodium ethiodronate (Difosfen, Rubio Laboratories) (n=23). All patients received 500 mg/12 hours of elemental calcium p.o. After 12 months of treatment, a significant increment of vertebral mineral density (VMD) was observed (6.4% and 8.2%, respectively). Serum BGP and PICP values remained elevated without a difference between the two drugs. Our results indicate that antiresorptive drugs may be of benefit in the high turnover osteoporosis of OLT recipients.

Journal ArticleDOI
TL;DR: In ex-weight lifters 50–64 years of age, the BMD was greater than in controls, and after 65 years, no difference was found between the former weight lifters and their controls.
Abstract: This cross-sectional study was done in order to ascertain whether there is a lifelong beneficial effect on bone mineral density (BMD) of early, long-lasting, and intense physical exercise. Forty-eight male ex-weight lifters, mean age 64 years (range 50-79) participated. They had followed a training program of an average of 10 hours/week (range 4-20) for an average of 13 years (range 1-34). They had all retired from competitive sport an average of 30 years (range 7-50) ago. Sixty-six age-matched volunteers served as controls. The bone mineral density (BMD, areal density, g/cm2) in the total body, spine, and hips and the fat content and lean body mass were measured with the LUNAR DPX bone mass scanner. In ex-weight lifters 50-64 years of age, the BMD was greater than in controls. After 65 years, no difference was found between the former weight lifters and their controls.

Journal ArticleDOI
TL;DR: A weak positive association was found between calcium intake estimates based on the food frequency questionnaire and total body BMD among premenopausal women and the preventive effect of high dietary calcium on osteoporosis is probably very weak.
Abstract: To determine the relationships among nutrients intake, bone mass, and bone turnover in women we have investigated these issues in a population-based, cross-sectional, observational study in one county in central Sweden. A total of 175 women aged 28-74 at entry to the study were included. Dietary assessment was made by both a semiquantitative food frequency questionnaire and by four 1-week dietary records. Dual energy X-ray absorptiometry was performed at five sites: total body, L2-L4 region of the lumbar spine, and three regions of the proximal femur. Serum concentrations of osteocalcin (an osteoblast-specific protein reflecting bone turnover) were measured by a radioimmunoassay. Linear regression models, with adjustment for possible confounding factors were used for statistical analyses. A weak positive association was found between dietary calcium intake as calculated from the semiquantitative food frequency questionnaire and total body bone mineral density (BMD) among premenopausal women. No association emerged between dietary calcium intake and site-specific bone mass, i.e., lumbar spine and femoral neck, nor was an association found between dietary calcium intake and serum osteocalcin. BMD at some of the measured sites was positively associated with protein and carbohydrates and negatively associated with dietary fat. In no previous studies of diet and bone mass have dietary habits been ascertained so carefully and the results adjusted for possible confounding factors. Neither of the two methods of dietary assessment used in this study revealed any effect of calcium intake on BMD at fracture-relevant sites among these healthy, mostly middle-aged women.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal ArticleDOI
TL;DR: The data suggest that VIT E protects against cellular lipid peroxidation in cartilage to sustain normal bone growth and modeling.
Abstract: The effects of dietary vitamin E (VIT E) and lipids on tissue lipid peroxidation and fatty acid composition, epiphyseal growth plate cartilage development, and trabecular bone formation were evaluated in chicks. A 2×2 factorial design was followed using two levels (30 and 90 IU/kg of diet) of dl-α-tocopheryl acetate and two different dietary lipids. The basal semipurified diet contained one of the following lipid treatments: anhydrous butter oil (40 g/kg)+ soybean oil (60 g/kg), [BSO], or soybean oil (100 g/kg), [SBO]. After 14 days of feeding, the level of α-tocopherol in plasma was higher and thiobarbituric acid reactive substances (TBARS) were less in plasma and liver of chicks supplemented with 90 IU of VIT E compared with those given 30 IU of VIT E. Body weights and tibiotarsal bone lengths were not affected by the dietary treatments Saturated fatty acids (14:0, 15:0, 16:0, 17:0, and 18:0) were increased in tibiotarsal bone of chicks fed the BSO diet. In contrast, total polyunsaturated fatty acids and the ratio of unsaturated fatty acids/saturated fatty acids were higher in plasma of chicks fed SBO compared with the values from chicks fed BSO. The thickness of the entire growth plate cartilage and the lower hypertrophic chondrocyte zone was significantly greater in chicks fed 90 IU/kg of VIT E. Kinetic parameters on bone histomorphometry indicated that mineral apposition rate was higher in chicks fed 90 IU/kg of VIT E. The interaction effect between the VIT E and BSO treatments led to the highest trabecular bone formation rate among the groups. These data suggest that VIT E protects against cellular lipid peroxidation in cartilage to sustain normal bone growth and modeling.

Journal ArticleDOI
TL;DR: It was concluded that rhBMP-2 has a strong osteoinductive potential and, in contrast to what was found earlier with other types of BMP preparations, this potential was retained when combining the rhB MP-2 with the osteopromotive membrane technique, yielding better bone healing than with the membrane alone, and at the same time maintaining the bone contour.
Abstract: It has been shown earlier that it is possible to improve bone healing, to regenerate previously existing bone, and to create new bone by means of an osteopromotive membrane technique. The present study addresses the question of whether it is possible to combine this technique with a locally applied factor, stimulatory to osteogenesis. Circular transosseous ‘critical size’ defects in mandibles of rats were either implanted with recombinant human bone morphogenetic protein type 2 (rhBMP-2) or were left empty; half the number of implanted and half the number of empty defects were covered with an expanded polytetrafluoroethylene (e-PTFE) membrane (GORE-TEX®). Results were evaluated after 12 and 24 days of healing by a histomorphological scoring system. Implantation of rhBMP-2 alone resulted in bony bridging of the defect after only 12 days, but also in voluminous amounts of new bone outside the original defect area. When rhBMP-2 was combined with membrane, newly formed woven bone bridged the defect and the bone contour was maintained by the membrane. The combined treatment with membrane and rhBMP-2 demonstrated a significantly better bone healing than with e-PTFE membrane alone at both 12 days and 24 days of healing. It was concluded that rhBMP-2 has a strong osteoinductive potential and, in contrast to what was found earlier with other types of BMP preparations, this potential was retained when combining the rhBMP-2 with the osteopromotive membrane technique, yielding better bone healing than with the membrane alone, and at the same time maintaining the bone contour. This combination may have important therapeutic applications for osseous healing and in reconstructive surgery. The study also shows the importance of an appropriate carrier material when applying stimulatory substances to enhance bone formation in combination with a membrane.

Journal ArticleDOI
TL;DR: Using low-dose glucocorticoids have increased rates of bone loss at appendicular sites among both elderly women and men, and after adjusting for confounding variables such as age and use of thiazides and estrogens.
Abstract: Although high doses of glucocorticoids are believed to cause bone loss, the effects of low glucocorticoid doses are still controversial. Our study examined the effects of low-dose glucocorticoids on the rate of bone loss at three appendicular bone sites. The study population was a cohort of elderly Japanese-Americans, 1094 women and 1378 men. The women were all postmenopausal. At the baseline examination the mean age of the women was 64 years (range 45–81), and the mean age of the men was 68 years (range 61–82). Glucocorticoid users (19 women and 21 men) had used oral systemic or inhaled glucocorticoids on a regular schedule for more than 1 month (mean use was 2.1 years for the women and 1.9 years for the men). The most common dose was equivalent to 5 mg/day of prednisone; fewer than 15% of users had taken doses equivalent to 10 mg/day or more. Changes in bone mass at the calcaneus, distal radius, and proximal radius were documented using bone densitometry at 1 to 2-year intervals over an 8-year period. The initial bone mass of the glucocorticoid users and controls was similar at the baseline examination. The subsequent loss rates among females during glucocorticoid use, however, were approximately double that of the controls. Among males, bone loss rates during glucocorticoid use were 2–3 times that of controls for the calcaneus and radius sites. The differences between glucocorticoid users and controls persisted after adjusting for confounding variables such as age and use of thiazides and estrogens. We conclude that users of low-dose glucocorticoids have increased rates of bone loss at appendicular sites among both elderly women and men.

Journal ArticleDOI
TL;DR: PQCT may be a reasonable surrogate for measurements by histomorphometry in studies of rat bone metabolism, and all three methods can demonstrate the effect of orchiectomy on trabecular bone.
Abstract: In studies of rat bone metabolism, trabecular bone density should be measured. Three established methods of measuring trabecular bone include trabecular bone volume by histomorphometry (BV/TV%), trabecular bone density by peripheral quantitative computerized tomography (pQCT), and areal bone density of trabecular-rich regions by dual x-ray absorptiometry (DXA). We compared the ability of these three methods to discriminate between orchiectomized (orchidectomized) rats and controls. Sixteen male Sprague-Dawley rats (400–425 g) were orchiectomized, and 16 others were controls. In vivo spine bone mineral density (BMD) was measured at the beginning of the study and again after 11 weeks. Rats were sacrificed, and ex vivo BMDs of the right femur and tibia were measured by DXA, followed by trabecular bone density of the right proximal tibia by pQCT. BV/TV% of the left proximal tibia was measured by histomorphometry. Differences between groups were detected by all three methods, but both the magnitude of the difference between groups and the variance of the measurements was much greater for histomorphometry and pQCT than for DXA. Consequently, the statistical significance for the difference between groups was comparable for all three methods. Of the sites measured with DXA, the proximal tibia had the greatest statistical significance for the difference between groups. In summary, all three methods can demonstrate the effect of orchiectomy on trabecular bone. The large differences between groups seen by histomorphometry are also seen by pQCT but not by DXA. We conclude that trabecular bone density by pQCT may be a reasonable surrogate for measurements by histomorphometry.

Journal ArticleDOI
TL;DR: Normative data for qualitative ultrasound measurements: speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness were established in 118 healthy women aged 20–86 years and in 42 healthy men aged 22–76 years and the relations between age, weight, height, and QUS were studied.
Abstract: Normative data for qualitative ultrasound (QUS) measurements: speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness were established in 118 healthy women aged 20-86 years and in 42 healthy men aged 22-76 years. The relations between age, weight, height, and QUS were studied. QUS measurements were negatively correlated with age in both sexes. In women, age was accepted as first factor (R2 = 0.39 for SOS, 0.35 for BUA, and 0.45 for stiffness, P < 0.001); weight was accepted as second factor for BUA (R2 = 0.44, P < 0.001). In men, age was the only significant parameter (R2 = 0.41 for SOS, 0.39 for BUA, 0.43 for stiffness, P < 0.001). QUS measurements of the right and left feet were highly correlated unless unilateral foot pathology such as algodystrophy was present. Significant correlations were found between QUS of the calcaneus and dual X-ray absorptiometry (DXA) of the lumbar spine (R = 0.67, P < 0.01 for SOS; R = 0.57, P < 0.02 for BUA; R = 0.65, P < 0.01 for stiffness).

Journal ArticleDOI
TL;DR: The results indieate that life-style factors such as smoking and coffee consumption decrease the serum concentration of intact PTH, and the same effects is seen in individuals with low body mass index.
Abstract: Intact parathyroid hormone (PTH) in serum was determined in a random population sample and was related to age, sex, body composition, life-style factors, blood pressure, blood lipids, plasma fibrinogen, and serum IGF-1, osteocalcin, and vitamin D. Within the framework of the WHO MONICA Project in the city of Goteborg, Sweden, 181 men and 166 women aged 25–64 years were studied. Intact PTH concentrations varied with age but were similar in both sexes trange 4–82 ng/liter) [mean (±SD) 23.8±10.4 ng/liter in men and 25.1±10.6 ng/liter in women]. Intact PTH concetrations increased with increasing age, body mass index, systolic blood pressure, and 1,25(OH)2D3 and decreased with increasing 25(OH)D3 in all subjects. Additionally, in men, intact PTH correlated positively to diastolic blood pressure and negatively to coffee consumption. In women, PTH also correlated negatively to smoking and IGF-1. In a multivariate analysis including all variables, age lost its significance. In both sexes there were independent positive relations between intact PTH and body mass index and 1,25(OH)2D3, and negative relations between PTH and smoking habits as well as 25(OH)D3; among men there was also negative relations between PTH and coffee consumption. The results indieate that life-style factors such as smoking and coffee consumption decrease the serum concentration of intact PTH, and the same effects is seen in individuals with low body mass index. Coffee intake, smoking, and low body mass index are also known to adversely affect bone mineral content, high-lingting the relationship between PTH and bone metabolism.

Journal ArticleDOI
TL;DR: The results of these quantitative measurements revealed an age-related decrease in the femoral cortical content of IGFBP-5, and comparisons with previous measurements of insulin-like growth factor-1 (IGF-I) and transforming growth factors-β (TGF-β), in extracts of the same bones showed significant cross-correlations.
Abstract: The skeletal contents of insulin-like growth factor-2 (IGF-II), insulin-like growth factor binding protein-5 (IGFBP-5), and insulin-like growth factor binding protein-3 (IGFBP-3) were determined in duplicate samples of human femoral cortical bone obtained from 64 subjects (44 males and 20 females) between the ages of 20 and 64 years The results of these quantitative measurements revealed an age-related decrease in the femoral cortical content of IGFBP-5 (r=-0272, P=0031) in the total population Although the femoral cortical content of IGF-II did not show a similar decrease with age, it could be correlated to the femoral cortical content of IGFBP-5 (r=0442, P<0001) In constrast, the femoral cortical content of IGFBP-3 did not decrease with age and could not be correlated to the femoral cortical contents of either IGFBP-5 or IGF-II Comparisons of these results with previous measurements of insulin-like growth factor-1 (IGF-I) and transforming growth factor-β (TGF-β), in extracts of the same bones, showed significant cross-correlations between the femoral cortical contents of each of these growth factors and the femoral cortical contents of IGFBP-5 (r=0625 for IGF-I versus IGFBP-5, r=0554 for TGF-β versus IGFBP-5, P<0001 for each) but not IGFBP-3 Together, these data indicate average net losses of 60% and 29% of the femoral cortical contents of IGF-I and IGFBP-5, respectively, and apparent net losses (ie, nonsignificant decreases) of 21% and 25% of the femoral cortical contents of IGF-II and TGF-β, respectively, between the third and the sixth decades (ie, decreases from young adult values of 751 pmol/g of bone for IGF-I, 1247 pmol/g of bone for IGF-II, 071 pmol/g of bone for TGF-β, 1156 pmol/g of bone for IGFBP-5, and 262 pmol/g of bone for IGFBP-3)

Journal ArticleDOI
TL;DR: The clonogenic stromal cells which are present in the bone marrow and are characterized by high proliferative and osteogenic potencies are discussed, and it has been found that in cultures of mice and guinea pig marrow cells, the efficiency of CFU-f colony formation decreases with aging.
Abstract: In this brief paper, I will discuss the clonogenic stromal cells which are present in the bone marrow and are characterized by high proliferative and osteogenic potencies. These cells were first detected in bone marrow cell cultures by their ability to form fibroblast colonies which are cell clones originating from single stromal cells (CFUO [1]. In vivo CFU-f remain arrested in the Go-period of the cell cycle [2], whereas in primary cultures of marrow cells they start to proliferate and form CFU-f-derived colonies-clones composed of marrow stromal fibroblasts. Approximately 50% of CFU-f colonies respond to parathyroid hormone by increases in adenylate cyclase activity [3] which is an accepted characteristic of the osteogenic phenotype [4]. CFU-f colonies can be passaged in vitro as multior single colony-derived fibroblast strains. Each single colonyderived strain is composed of the descendants of one CFU-f, and the conclusive proof of high proliferative and osteogenic potencies of CFU-f were obtained by passaging these strains in vitro and by their transplantation in diffusion chambers (DC). It was found that descendants of single CFU-f can accomplish more than 20 population doublings in vitro and at transplantation in DC they can simultaneously form bone, cartilage and reticular tissue, or only bone or only reticular tissue [5]. This demonstrates heterogeneity of CFU-f, some of them being the osteogenic stem cells, and the others committed precursors for bone or for marrow reticular cells. CFU-f colonies may also be transplanted heterotopically in Gelfoam sponges. In such experiments, some of the colonies form bone organs with medullar cavity populated by hemopoietic cells which means that hemopoietic microenvironment can be transfered by one CFU-f. Regarding the CFU-f in connection with aging problems, it has been found that in cultures of mice and guinea pig marrow cells, the efficiency of CFU-f colony formation decreases with aging. It seems to be an interesting and important point, however, only now can it be definitely interpreted. The decrease may depend on different reasons, not necessarily on reduction of CFU-f concentration in the marrow. For example, it can depend on lower sensitivity of CFU-f from older donors to growth factors which push CFU-f from the Go period of the cell cycle into proliferation in cultures. This and other possible explanations can be determined by the CFU-f colony assay. According to my knowledge, no data have been published concerning age-related changes of CFU-f in humans, including their concentration in the marrow and possible

Journal ArticleDOI
TL;DR: It is proposed that the process of cellular recruitment in aseptic loosening is initiated when the mechanical failure of the cement mantle leads to the production of PMMA particles, which are phagocytized by macrophages leading to the release of TNF.
Abstract: The association of macrophages engaged in polymethylmethacrylate (PMMA) particle phagocytosis with pockets of inflammatory cells is a pathognomonic feature of the aseptically loose interface not present at the well-fixed interface. The mechanism by which the presence of PMMA particles leads to cellular recruitment, bone resorption, and ultimate loosening is poorly understood. Granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin 6 (IL-6), cytokines released by osteoblasts, stimulate the recruitment of macrophages into sites of inflammation. We show that exposure of macrophages to PMMA particles stimulated release of tumor necrosis factor (TNF), but no increase in prostaglandin E2 (PGE-2) or interleukin 1. Incubation of osteoblasts with conditioned medium from macrophages exposed to PMMA particles led to release of GMCSF, IL-6, and PGE-2. Incubation of the PMMA/macrophage medium with antibodies to TNF prior to osteoblast exposure inhibited release of GM-CSF, IL-6, and PGE-2 by the osteoblasts. Our data demonstrate that exposure of macrophages to PMMA particles leads to the release of TNF which then stimulates osteoblasts to produce GMCSF, IL-6, and PGE-2. Based upon the results of this study, we propose that the process of cellular recruitment in aseptic loosening is initiated when the mechanical failure of the cement mantle leads to the production of PMMA particles. These particles are phagocytized by macrophages leading to the production of TNF. TNF stimulates surrounding osteoblasts to produce GM-CSF, IL-6, and PGE-2 which leads to recruitment of macrophages and osteoclasts into the area of the bone-cement interface. The recruitment of these cells potentiates this process leading to bone resorption and ultimately, clinical loosening of prosthetic joint implants.

Journal ArticleDOI
TL;DR: It is suggested that salmon calcitonin is effective in the treatment of osteoporosis and show that it acts on cortical and trabecular bone.
Abstract: Seventy-two postmenopausal osteoporotic women having more than one nontraumatic vertebral crush fracture were studied. Thirty-six of them, aged 68.8±1.2 years (18±4 YSM-years since menopause), were treated with 100 IU/day of salmon calcitonin i.m. plus 500 mg of elemental calcium for 10 days each month. The remaining 36 patients, aged 69.6±1.4 years (19±3 YSM), were given only 500 mg of elemental calcium for 10 days each month. All patients underwent clinical and analytical evaluation every 3 months. Radiological evaluation, assessment of vertebral deformities, and metacarpal radiogrammetry were done every 6 months. Densitometric measurements of total and regional bone mass were made every 12 months. At 24 months, the calcitonin group showed a 60% reduction in the number of new fractures and the group receiving only calcium had a 45% increase (P<0.001). The incidence of vertebral fractures was 0.07 per patient-year in the group treated with calcitonin and 0.45 per patient-year in the group treated with calcium (P<0.001). At 2 years, the calcitonin group showed a 12% increase in cortical bone mass on metacarpal radiogrammetry, a 16% increase in the axial skeleton on trunk densitometry, a 3.5% increase in total body bone mineral content, a 30.7% increase in pelvic bone mineral content, and a 6.2% increase in arm bone mineral content (all P<0.001). In the group treated with calcium alone there was a loss of bone mass in every region. These findings suggest that salmon calcitonin is effective in the treatment of osteoporosis and show that it acts on cortical and trabecular bone.

Journal ArticleDOI
TL;DR: It is concluded that measurement of a single proximal femur will usually be sufficient for clinical evaluation of BMD and/or hip axis length, and bilateral BMD measurements are indicated in subjects where unilateral degeneration or disease are suspected.
Abstract: Dominant/nondominant differences in bone mineral density (BMD) have been observed in the upper extremities. However for the proximal femur, the distinction between dominant and nondominant hips is not clear. The purpose of this study is to evaluate left/right variations in femoral BMD and hip axis length (HAL) in both single beam and fan beam dual x-ray absorptiometry (DXA) scans. A total of 36 women aged 41–76 years (average age 60±10 years) received single beam and fan beam DXA scans of both proximal femora with a Hologic QDR-2000 scanner. Femoral BMD and hip axis length were determined for each scan. Left/right and single beam/fan beam correlations were determined and differences were evaluated using a two-way analysis of variance. Femoral BMD at corresponding measurement regions in opposing femora were highly correlated (r=0.81–0.96). No significant left/right differences were detected. At the femoral neck, the mean BMD difference (± standard deviation) was 1.5%±4.7% in a single beam mode and-0.6%±6.3% in fan beam mode. Though mean values of femoral BMD were equivalent, the observed individual left/right differences were occasionally large (as high as 26% in the femoral neck). The hip axis length of the left and right hips were highly correlated and statistically equivalent. However, hip axis length using fan beam was significantly larger (7.5%) than the single beam measurement with a larger observed variation. We conclude that measurement of a single proximal femur will usually be sufficient for clinical evaluation of BMD and/or hip axis length. However, bilateral BMD measurements are indicated in subjects where unilateral degeneration or disease are suspected. If possible, hip axis length should be measured in single beam mode to avoid magnification errors.

Journal ArticleDOI
TL;DR: Although calcitonin has an established place in the treatment of Paget's disease of bone and certain disorders of calcium homeostasis, its most exciting clinical application is in the management of postmenopausal and senile osteoporosis.
Abstract: Although calcitonin has an established place in the treatment of Paget's disease of bone and certain disorders of calcium homeostasis, its most exciting clinical application is in the management of postmenopausal and senile osteoporosis. This disorder affects a vast number of women and, with the increasingly aging population, imposes a heavy burden on health care systems. Although other therapies for osteoporosis and other disorders of bone turnover (e.g., bisphosphonates, fluoride) are in use, many questions remain to be answered concerning their side effects and long-term safety, whereas salmon calcitonin is of proven safety. The introduction of salmon calcitonin nasal spray is a significant therapeutic advance, and the development of other noninjectable preparations will further increase the acceptability of calcitonin to patients and physicians alike.

Journal ArticleDOI
TL;DR: Bone sialoprotein bound to the α 2 chain within the hole zones may regulate the onset of calcification at hole zones and the cell binding to collagen fibrils.
Abstract: Bone sialoprotein (BSP) has an affinity to collagen fibrils [25]. A role of carbohydrate chains in the affinity was examined by removing sialic acids of BSP. Neuraminidase treatment of the BSP increased the binding to collagen. Binding sites of BSP on collagen were examined by biochemical and electron-microscopic methods. Purified bovine BSP was labeled with biotin. Collagen α chains or CNBr peptides were separated by electrophoresis and transfered to nitrocellulose membranes. The membranes were incubated with the biotin-labeled BSP, and the bound BSP was visualized with avidin conjugated with alkaline phosphatase. The labeled BSP was preferentially bound to the α 2 chain, and peptides derived from α 2 chain. In another experiment, the labeled BSP was incubated with reconstituted native collagen fibrils. The mixture was put on a copper grid, reacted with avidin conjugated with gold particles, and observed with an electron microscope. The gold particles were seen mainly within hole zones of the fibrils. BSP bound to the α 2 chain within the hole zones may regulate the onset of calcification at hole zones and the cell binding to collagen fibrils.

Journal ArticleDOI
TL;DR: It is suggested that in women with hip fractures, ultrasound evaluation of the os calcis has diagnostic sensitivity comparable to DXA of the femur and could be useful to predict hip fracture risk.
Abstract: To assess the usefulness of the measurement of the os calcis by ultrasound, a method that probably reflects bone quality as well as density, we have studied 54 women with hip fracture of the proximal femur and a control group. Ultrasound evaluation of the os calcis [broadband ultrasound attenuation (BUA), speed of the sound (SOS), and a combined index (“stiffness”)], and bone mineral density (BMD) determination over the proximal femur by dual X-ray absorptiometry (DXA) were performed. Weight, BMD, and ultrasound values in the hip fracture patients were significantly lower than controls (P<0.001). The Z-scores for BUA and stiffness were not different than that for femoral neck. Ward's triangle or trochanteric BMD (between-1.7 and -1.5). The odds ratios determined by receiver-operating characteristics (ROC) analysis were greater at the femoral neck (25.1) and BUA (24.4). Intermediate values were found at stiffness (16.9), Ward's triangle (12.8), and trochanter (11.1), and lower values were obtained at SOS (4.2). In turn, patients with trochanteric hip fractures had a significantly lower femoral neck and Ward's triangle BMD, stiffness, and BUA than patients with cervical hip fractures. Comparing a subgroup of 30 women with hip fractures without vertebral fractures with an age-matched group of 87 women with osteoporotic vertebral fractures, both groups were of similar weight and BMD but all ultrasound values were significantly lower in the hip fractures compared with vertebral fracture patients (P<0.05-P<0.01). Our findings suggest that in women with hip fractures, ultrasound evaluation of the os calcis has diagnostic sensitivity comparable to DXA of the femur and could be useful to predict hip fracture risk. Ultrasound values are lower in hip fractures compared with vertebral fracture, age-matched women and in older compared with younger hip fracture patients.

Journal ArticleDOI
TL;DR: Bone mineral density (BMD) measured by dual X-ray absorptiometry in lumbar spine and proximal femur was sharply reduced at the initial visit, and remained unchanged during long-term follow-up on hormone replacement therapy with estrogens and progestin.
Abstract: The response of bone mass to long-term treatment with estrogen and progesterone in patients with complete androgen-insensitivity syndrome (AIS) is unknown. We report a 17-year-old female patient (karyotype 46 X, Y) with AIS studied during a 4-year period. Bone mineral density (BMD) measured by dual X-ray absorptiometry in lumbar spine and proximal femur was sharply reduced at the initial visit, and remained unchanged during long-term follow-up on hormone replacement therapy with estrogens and progestin. Bone metabolism markers were all in the normal range. The lack of significant increase in BMD highlights the importance of androgens on bone physiology that cannot be balanced in spite of an appropriate estrogenic milieu.

Journal ArticleDOI
TL;DR: Femoral rotation was shown to have a significant effect on BMD measurements, and proper positioning of the femur during a scan can improve precision significantly.
Abstract: Precision in femoral neck scans with dual energy X-ray absorptiometry (DXA) is affected by variability in positioning and subsequent repositioning of the femur for repeated scans. To study the in vitro effect of femoral rotation on the bone mineral density (BMD), four fresh-frozen cadaveric femurs were fixed in a specially designed jig which allows for rotation of the femurs. BMD measurements of the femurs were done in neutral position (0°) i.e., with the femoral neck axis parallel to the surface of the couch and at 15°, 30°, and 45° of internal and external rotation. In vivo precision of the femoral neck scan was determined in five normal male subjects. The scans were first done with the legs positioned using the manufacturer's foot block. Five scans were performed, with repositioning, on the left hip of each subject. The procedure was then repeated with the legs positioned using a custom-designed positioning jig to minimize the rotation of the hips during a scan. In the in vitro study, the femoral neck BMD value was minimum at neutral position (0°) and increased when the femur was rotated internally or externally. In vivo precision error of the femoral neck scan was reduced by almost 50% with the use of the positioning jig when compared with the manufacturer's foot block. Femoral rotation was shown to have a significant effect on BMD measurements, and proper positioning of the femur during a scan can improve precision significantly.