Endosteal Resorption Research Articles

Histomorphometric Characterization of Cancellous and Cortical Bone in an Ovariectomized Sheep Model

Giavaresi, G., Fini, M., Martini, L., Nicoli Aldini, N., Rocca, M., Torricelli, P. and Giardino, R. 2001. Histomorphometric characterization of cancellous and cortical bone in an ovariectomized sheep model. J. Appl. Anim. Res., 20:221–232. The ovariectomized sheep has been proposed as a model of human osteoporosis, showing high bone turnover, increased osteoclastic activity, perforation of trabeculae and endosteal resorption. To improve scientific knowledge on this large-size osteopenic animal model, 15 crossbred sheep (4±1 years, 80±5 kg) were divided in 3groups of 5 animals each: 1) Baseline Group, where animals were sacrificed at the beginning of the study as controls; 2) OVX Group, where animals were bilaterally ovariectomized. 3) SHAM Group, where the operation was simulated. OVX mid SHAM animals were sacrificed 24 months after surgery. A histomorphometric analysis was performed on cancellous (iliac crest, and 4th and 5th lumbar vertebral bodies) and cortical (femoral and libial middiaphyses) bone. In the OVX Group, results showed generalised and significant resorption of cancellous bone in the iliac crest and lumbar vertebrae, as well as significant resorption of cortical bone in the tibia. The cancellous bone of the vertebral bodies appeared to be more sensitive to the estrogen-deficiency than the iliac crest and the same can be said for the tibial middiaphyseal cortical bone versus the femoral one. In conclusion, our results seem to support the use of an ovariectomized sheep model for pharmacological and surgical studies on osteoporosis. However, differences in bone reaction to estrogen-deficiency at different anatomical sites should be taken into account and do require further investigations.

Effects of age and occupation on cortical bone in a group of 18th-19th century British men.

The effects of age and occupation on cortical bone in a group of adult males from the 18th-19th century AD skeletal collection from Christ Church Spitalfields, London, were investigated. Cortical bone was monitored using metacarpal radiogrammetry. Individual age at death was known exactly from coffin plates. Occupation for individuals was known from historical sources. Results showed that continued periosteal apposition was evident throughout adult life, but from middle age onwards this was outstripped by about 2:1 by endosteal resorption, so that there was net thinning of cortical bone. The rate of cortical thinning resembled that seen in modern European males. Cross-sectional properties, as measured by second moments of area, bore no relationship to occupation. The results may suggest that, firstly, patterns of loss of cortical bone have remained unchanged in males for at least two centuries in Britain, and secondly, that biomechanical analyses of metacarpal cortical bone may be rather insensitive indicators of intensity of manual activity.

Unresolved issues in osteoporosis in men.

Fragility fractures in men are a public health problem. The increasing longevity in men is likely to increase the public health burden of fractures in men. This problem remains unrecognized by doctors, the public and governments. About one third of all hip fractures occur in men but the incidence and gender ratio varies from country to country for reasons that are not understood. The prevalence of spine fractures is about half that of women in most studies, but similar to that of women in several other studies. The incidence of spine fractures is uncertain but is likely to be about half that of women except in 80+ year olds, when it appears to be similar. The causes of the higher mortality in men than in women following hip or spine fracture are not well defined. Areal bone mineral density (aBMD) predicts fracture risk in men; the relative risk for spine and hip fracture conferred by a 1 SD lower aBMD, or by a prevalent fracture, is similar in men and women. The age-specific absolute risk (number of cases per 1,000 per year) conferred by a given hip aBMD is similar in men and women. The age-specific absolute risk conferred by aBMD at the calcaneus or radius for spine fracture is similar for men and women. If the absolute and relative risks are similar then the lower incidence of fractures in men than women may reflect the lower proportion of the male population distribution below a given structural determinant of bone fragility. That is, at any age, there may be fewer men than women with smaller bones, lower volumetric bone mineral density (vBMD), thinner trabeculae or cortices, architectural disruption, or higher remodeling rates. Higher mortality and fewer falls may also contribute to the lower incidence of fractures in men. This tail end of the male population distribution (for traits like bone size, vBMD, architecture, and remodeling rates) is the likely source of fracture cases in males. Hypogonadism is a risk factor for osteoporosis. However, the definition, prevalence, causes and structural consequence of hypogonadism are inadequately defined. At what level of testosterone is bone balance negative? What structural determinants of axial and appendicular strength are regulated by testosterone, estrogen, growth hormone (GH), insulin like growth factor 1 (IGF-1) (or their interactions)? Is reduced bone size in men with spine or hip fractures due to failed growth-related or age-related periosteal expansion? If reduced vBMD is due to reduced accrual, is this due to reduced cortical thickness? What factors regulate and coregulate the periosteal and endocortical modeling and remodeling? Are reduced trabecular numbers due to failed formation at the growth plate, excess resorption of primary trabeculae or reduced formation of secondary trabeculae? Is reduced trabecular thickness due to failed prepubertal or pubertal bone formation? Is reduced cortical and trabecular thickness during aging due to excessive endosteal resorption or reduced bone formation? If the former, is this due to increased remodeling sites or increased resorption depth? Most evidence favors reduced bone formation as the cause of bone loss with trabecular bone loss occurring by reduced formation and thinning more than by increased resorption and loss of connectivity. Cortical bone loss is less than in women because endocortical resorption is less and periosteal apposition is greater. If the reduced bone formation is most important, is this due to reduced osteoprogenitors, reduced osteoblast matrix synthesis or early osteoblast apoptosis? Anti-spine-fracture efficacy has been demonstrated in only one randomized heated with alendronate drug in men. The gaps in our knowledge remain large.

A biomechanical enigma: why are tibial fractures not more frequent in the elderly?

Epidemiology revealed that diaphyseal fractures of the tibia affect young people, particularly young men; no increase was noticed for the elderly. This indicates that osteoporosis does not lead to increased bone fragility. Obviously, this is a biomechanical enigma. Torque measurements were carried out on human cadaveric tibiae and revealed a great correlation between the polar moment of inertia of the cortical bone at the tibial isthmus and the ultimate torque at failure (r = 0.83) and a lesser correlation between the cross-sectional density at the isthmus and the torque at failure (r = 0.57). Therefore, the size is more important than the degree of osteoporosis. We can speculate that endosteal resorption due to osteoporosis is compensated for by periosteal apposition and therefore does not lead to bone weakness.

Âge individuel, longévité et dynamique de croissance osseuse chez un amphibien vivipare, Nectophrynoides occidentalis (Anoure, Bufonidé)

Skeletochronology, used to assess some life history traits in the viviparous African toad, enables us to determine that longevity in natura does not exceed 5 years in females and reaches at least 2 years in males. After sexual maturity, reached at four months, the rate of osteogenesis decreases, as probably does body growth. In this study we discovered a strong endosteal bone resorption in long bone cortices in both males and females. This phenomena only occurs during the first resting period. This period occurs from October (individuals of 5 months old) to March (individuals of 10 months old). During this time toads are underground and their metabolism is thought to be low. The origin of such an endosteal resorption remains more or less unknown.

Role of Bone Bark During Growth in Width of Tubular Bones A Study in Human Fetuses

The morphologic features of bone bark, a structure surrounding the distal and proximal ends of long bones, were studied in the distal femur, proximal tibia, and proximal fibula of 77 spontaneously aborted human fetuses varying in gestational age from 10 to 20 weeks. Standard histologic techniques used in addition to in situ immunohistochemical staining allowed the examination of the structure of the bone bark and localization of Types 1, 2, and 3 collagens at different gestational ages. The bone bark was shaped like a cylindrical sheath of bone lamellae of varying thickness. The epiphyseal end of the bone bark, known as the groove of Ranvier, was covered outwardly by a fibrous layer and inwardly by the epiphyseal cartilage and contained mesenchymal cells, chondroblastic precursor cells, and densely packed cells differentiating into osteoblasts. Neither the cell density in the groove nor the thickness of the bone bark were identical circumferentially, indicating an unequal growth in width. In addition, the presence of periosteal apposition and endosteal resorption of the bone bark on one side and of endosteal bone deposition accompanied by periosteal resorption of the bone bark on the opposite side support the concept of a spatial drift of bones. These observations furnish histologic proof that groove and bone bark, although assuring an equal growth in length, contribute to an unequal and eccentric growth in width.

Skeletochronology and Geographic Variation in Age Structure in the Wood Frog, Rana sylvatica

Age structure of a breeding population of Rana sylvatica from southwestern Quebec, Canada, is described based on the enumeration and analysis of Lines of Arrested Growth (LAGs) in phalanges. Analyzed using skeletochronology, ages ranged from 1-4 yr among 98 males and from 2-4 yr among 33 females. Females were on average slightly older than males, but the difference was not significant. Mean snout-vent length was 43.6 mm ? 2.0 (SD) among 179 males and 48.8 mm ? 2.7 among 33 females; the difference between the sexes was significant. Endosteal resorption completely destroyed LAG 1 in 6.1% of frogs, about twice as frequently in males as in females. A minimum of three LAG enumeration readings by two observers differed for 24.4% of preparations and independent readings by the same observer differed for 15.3% of preparations, highlighting the importance of reducing subjectivity in skeletochronological anal- yses. This was accomplished, in part, by plotting LAG diameters on a histogram whereby outliers from an expected normal distribution indicated loss of inner LAGs via endosteal resorption. Consistent with pre- dictions regarding environmental influences on anuran populations, southern Quebec R. sylvatica matured later and were larger than more southerly conspecifics from a low-elevation area, but matured earlier and were smaller than southerly frogs from a high-elevation area. Interpopulational variation in life history

Bone Measurements in Asymptomatic Primary Hyperparathyroidism

A large proportion of patients with asymptomatic primary hyperparathyroidism (PHPT) have some degree of bone involvement which appears to be relatively greater for cortical than trabecular bone. However, the clinical meaning and pathophysiologic basis of this observation are unknown. In 77 postmenopausal women with asymptomatic PHPT, bone mineral density (BMD) was measured at the proximal and ultradistal forearm, the lumbar spine, the femoral neck, and Ward’s triangle by dual-energy X-ray absorptiometry. The digitalized X-ray pictures of the nondominant hand were obtained from all patients and from 680 healthy postmenopausal women, to measure the outer ( D) and inner ( d) diameter of the second metacarpus. The cortical area per total area (CA/TA) and a bending breaking resistance index ( D 4– d 4/ D) were then calculated. In 29 of the patients not operated on and in 30 healthy pair-matched women, a second X-ray of the hand was obtained 5–12 years afterward. In patients with PHPT, the z score of CA/TA was significantly lower than zero [−0.97 ± 0.99, standard deviation (SD)]. This is due to an enlargement of the inner diameter, despite a significant increase in the z score for the outer diameter. The z score of the DXA measurements was significantly lower than zero for the lumbar spine (−0.59 ± 1.26), ultradistal radius (−1.03 ± 0.91), proximal radius (−1.91 ± 1.80), and Ward triangle (−1.81 ± 1.07), but not for the femoral neck (−0.36 ± 1.03). In subjects in whom two X-rays were obtained, per-decade endosteal resorption and periosteal apposition were statistically significant only in the PHPT patients. Both endosteal resorption and periosteal apposition were significantly greater in PHPT patients compared to healthy controls. The mean BBRI in PHPT patients was not different from that in controls, but the longitudinal changes were significantly greater than those observed in control subjects. Our radiogrammetry data may provide an original clue for understanding preferential cortical bone loss in PHPT patients. In cross-sectional and longitudinal studies, we have shown that in PHPT, both endosteal bone resorption and periosteal apposition are augmented. The former effect is predominant, which leads to significant diminution of cortical thickness. As a consequence of the enlargement of long bones, the areal BMD is somewhat underestimated, since the same amount of cortical bone is divided by a greater diameter. Furthermore, in term of mechanical properties, the increases in the cross-sectional area of appendicular bone segments might compensate in part for both the diminution of cortical thickness and a greater porosity of cortical bone.

Bisphosphonate Maintains Parathyroid Hormone (1-34)-Induced Cortical Bone Mass and Mechanical Strength in Old Rats

This study was designed to determine the fate of new parathyroid hormone (PTH)-induced cortical bone after withdrawal of PTH treatment, and to evaluate whether subsequent treatment with a bisphosphonate would influence this. Six groups of 21-month-old rats were used: a baseline group killed at the beginning of the experiment, three groups injected with human PTH (1-34) (62 mug/kg) daily for 8 weeks (day 1-56), then one group was killed and the other two groups were injected for another 8 weeks (day 57-112) with either saline or bisphosphonate (risedronate 5 mug/kg twice a week). Two control groups were injected with vehicle for the first 8 weeks, then one group was killed and the other group injected with saline the next 8 weeks. All animals were labeled with tetracycline and calcein on day 35 and day 49 of the experiment, respectively. PTH increased periosteal (35%) and in particular endosteal mineralizing surfaces (188%), mineral appositional rates, and bone formation rates at the femur diaphysis, leading to an increase in cortical cross-sectional area of 31%. Withdrawal of PTH induced a fast and pronounced endosteal bone resorption whereas risedronate prevented this resorption. No differences were seen in apparent density of dry defatted bone and ash among the groups. PTH increased the mechanical strength of the femur diaphysis; ultimate load increased by 64% and ultimate stress by 25%. A pronounced decrease in mechanical strength and competence was found after withdrawal of PTH: ultimate load decreased by 31% and ultimate stress by 21%. Risedronate, however, prevented this decrease in mechanical strength and competence in these 2-year-old rats.

AGE TRENDS IN REMODELING OF THE FEMORAL MIDSHAFT DIFFER BETWEEN THE SEXES

Cross-sectional area properties of the femoral midshaft from 203 individuals of known height and weight, 1–97 years of age, from a modern Australian population were quantified using automatic video image analysis. The aim of this study, taking height and weight into account, was to determine whether (a) age trends in remodeling differ between the sexes, (b) men are better able to compensate for bone loss with age, and (c) this protective mechanism is carried through into old age. Our findings indicated that during adulthood there are distinct gender differences in femoral remodeling. From around the third to the seventh decade, men showed a fairly uniform increase in subperiosteal area, polar moment of inertia, and medullary area. Women displayed two distinct phases during this period: relative stability until around the menopause and then a marked increase in all of the above variables. In old age, gender differences diminished, both sexes showing reduced periosteal apposition and increased endosteal resorption. The resultant decline in cortical area of approximately 4% in men and 15% in women from the third to the eighth decade was significant only in women. For a given height, men had larger, stiffer femoral shafts with a greater cortical width and area and maintained this advantage into old age. Diaphyseal bone was not immune from age-related changes affecting other skeletal sites; however, due to compensatory remodeling, which was particularly evident in men, this was not reflected in increased fracture rates.

Comparison between direct radiographic enlargement and mammography technique in detection of osseous changes of the hand skeleton in hyperparathyroidism

To compare direct magnification radiography and mammographic film-screen systems in osseous changes of the hand in hyperparathyroidism. The hands of 60 patients who were suspected to have primary (5), secondary or tertiary (both 55) hyperparathyroidism were evaluated with direct magnification radiography and a mammographic film-screen system (S12.5). Posterior-anterior views of each hand were obtained with both techniques. The magnification radiographs were made with a focal spot size of 40 or 60 microns, digital luminescence radiography (S600/1200), and a x 6 or 8 magnification. The 240 films were evaluated for subperiosteal, intracortical and endosteal resorptive changes by five radiologists using a grading according to five levels of confidence. A significant improvement (p < 0.05) in the diagnosis of periosteal and intracortical bone resorption was shown, but no significant changes in endosteal resorption with direct magnification radiography. As compared to mammographic film-screen systems, magnification radiography improved the diagnostic accuracy (24%). The time needed for the evaluation of periosteal and intracortical bone resorption was shortened with direct magnification radiography (-4%/ -15%), and the time for giving the diagnosis decreased (-10%).

Changes in femoral cortical dimensions after uncemented revision hip arthroplasty: Radiological results with the porous-coated Bi-Metric femoral stem prosthesis in 15 asymptomatic cases

The radiographic results of 15 uncemented femoral revisions after a minimum follow-up period of 2 years are reported. Digital imaging was used to quantify the remodeling of the cortical bone. A method using computer-assisted video densitometry was developed and radiographs were scanned and digitized by a computer. The femoral cortex in five regions, as well as the endosteal diameter, was determined. After rearthroplasty, there was a significant loss in cortical bone with widening of the medullary canal. The periosteal diameter did not change. This endosteal resorption could contribute to further aseptic loosening. In addition, it could be an explanation of the primary prosthetic failure; one mode of failure could be an accelerated rate of endosteal expansion in a subgroup of the general population after hip arthroplasty.

Age trends in remodeling of the femoral midshaft differ between the sexes.

Cross-sectional area properties of the femoral midshaft from 203 individuals of known height and weight. 1-97 years of age, from a modern Australian population were quantified using automatic video image analysis. The aim of this study, taking height and weight into account, was to determine whether (a) age trends in remodeling differ between the sexes, (b) men are better able to compensate for bone loss with age, and (c) this protective mechanism is carried through into old age. Our findings indicated that during adulthood there are distinct gender differences in femoral remodeling. From around the third to the seventh decade, men showed a fairly uniform increase in subperiosteal area, polar moment of inertia, and medullary area. Women displayed two distinct phases during this period: relative stability until around the menopause and then a marked increase in all of the above variables. In old age, gender differences diminished, both sexes showing reduced periosteal apposition and increased endosteal resorption. The resultant decline in cortical area of approximately 4% in men and 15% in women from the third to the eighth decade was significant only in women. For a given height, men had larger, stiffer femoral shafts with a greater cortical width and area and maintained this advantage into old age. Diaphyseal bone was not immune from age-related changes affecting other skeletal sites: however, due to compensatory remodeling, which was particularly evident in men, this was not reflected in increased fracture rates.

Identification of macrophage migration inhibitory factor in synovial membranes of loosened total joint replacement.

Endosteal bone resorption often occurs around loosened total joint replacements. In the process of the loosening, macrophages play an important role by releasing cytokines such as interleukin-1, tumor necrosis factor-alpha and prostaglandin E2. In this study, we investigated the involvement of macrophage migration inhibitory factor (MIF) in the pathological state of the loosening of a total hip replacement. Interface membranes were harvested from bone-cement or bone-implant interfaces of two patients during revision hip surgeries. The tissues were immunohistochemically examined with a polyclonal antibody against human recombinant MIF. This study detected MIF in the cytoplasm of the macrophages in all the tissues tested, though it was not detected in that of interstitial cells. The expression of MIF mRNA in the membrane was also examined by reverse transcription polymerase chain reaction, which demonstrated that expression of the MIF mRNA in the interface membranes was higher than that of the normal synovium. Considering these results, it is suggested that MIF is one of important cytokines mediating the inflammatory process during loosening of total joint replacements.

Present and future of osteoporosis therapy

In the 50-year “modern” history of osteoporosis, there have been about 17 antifracture studies with sufficient attention to design to allow inference regarding efficacy. Antivertebral fracture efficacy has been reported with etidronate, estrogen patch, calcitonin, and 1,25-dihydroxyvitamin D. Two studies using fluoride were positive, and two were negative. Hip fractures have been neglected. One study showed efficacy of hip protectors, one showed efficacy of vitamin D and calcium in nursing home dwellers. The source of most hip fractures is the community. One community based antihip fracture efficacy study using annual injections of vitamin D was positive. There have been no antivertebral or antihip fracture studies in men, or in corticosteroid-related osteoporosis in men or women. Lack of independently repeated demonstration of efficacy, small fracture numbers, and data pooling in some of these (the best) studies leave great uncertainty. Estrogen and bisphosphonates appear to be the best options at this time. New data suggest that calcium supplementation is likely to reduce the rate of bone loss and perhaps reduce fracture rates. The challenge is to maintain and restore the constituents of bone mineral density (BMD), that is: to promote periosteal and endosteal bone formation; reduce endosteal bone resorption and cortical porosity; and increase trabecular thickness, number, and connectivity. There are many opportunities, for instance, intermittent parathyroid hormone (PTH) increases bone strength and, with estrogen, may increase connectivity. The anabolic effects of PTH may be partly mediated by IGF-1. IGF-1 increases periosteal, endosteal, and trabecular bone formation, cortical and trabecular width, and trabecular and endocortical connectivity. With bisphosphonate, IGF-1 may increase bone area and strength as the bisphosphonate decreases medullary area while IGF-1 increases subperiosteal area. Anabolic effects of fluoride warrant further study provided that the study design addresses the issue of bone strength, the narrow toxic-therapeutic window, and cortical bone loss. Aluminum, a constituent of zeolite, has anabolic effects which may be partly mediated by TGF-β. Prostaglandin E2 increases periosteal and endosteal bone formation but may increase cortical porosity. More data are needed regarding these growth factors, silicon compounds, strontium salts, and flavenoids. The effects of medroxyprogesterone and 19 norprogestins on BMD have not been compared. Raloxifene, a new estrogen agonist free of endometrial hyperplastic effects, is being studied. Most treated individuals with osteoporosis (i.e., low BMD with or without a fracture) will not suffer a fracture so treatment must be safe. Success—absence of fracture—will be measured by the epidemiologist because it is difficult to distinguish efficacy from chance in an individual as the peak incidence of fractures in the community is usually only about 1–4/100 per year.

Craniofacial bone remodeling in growing rats fed a low-calcium and vitamin-D-deficient diet and the influence of masticatory muscle function.

Fifty-two male growing rats were randomly divided into three groups. The first group (n = 18) received a hard deficient diet, and the second (n = 18) a soft deficient diet. The control group (n = 16) was fed the normal hard diet. At the beginning and in the middle of the 28-day experimental period oxytetracycline was injected. Two representative coronal sections of the snout and the corresponding contact microradiographs were analyzed. The bone mass of the premaxillary and nasal bones seemed to be less in the two deficient diet groups than in the normal one, due to an increased endosteal bone resorption and decreased bone formation. No difference in the bone apposition rate and pattern could be seen between the deficient hard and soft diet groups, except in the dorsal part of the premaxilla, where the bone formed in the first half of the experiment was markedly more resorbed in the deficient soft diet group during the remaining period than in the deficient hard diet group. The morphology of the sutures was influenced by the altered function, since the sutural space became narrower, and premature obliterations of the internasal suture were observed in the deficient soft diet group. In conclusion, poor bone quality was observed in the skull of rats fed a low-calcium and vitamin-D-deficient diet, with less bone mass than in normal conditions. Masticatory function was a significant factor influencing bone remodeling and sutural growth even in situations in which a metabolic bone disturbance exists.

Modeling hand phalanx endosteal bone resorption: An investigation with us

Modeling hand phalanx endosteal bone resorption: An investigation with us

Age Determination of the Stream Frog, Rana sakuraii, by Skeletochronology

In long-lived species such as amphibians, age determination of individual animals is important in elucidating population dynamics and life histories. Although four methods have been used for aging amphibians, only skeletochronology and mark-recapture are reliable (see Halliday and Verrell, 1988). Markrelease-recapture potentially provides the most reliable data on age, but this method is very labor-intensive and takes a long time to yield a result. On the other hand, skeletochronology using phalanges has proved to be an excellent tool to investigate population age structure. Although this method has potential problems (such as endosteal resorption of periosteal bone which may alter the early year rings), many studies have been conducted successfully using skeletochronology in anurans (e.g., Hemelaar and van G lder, 1980; Gibbons and McCarthy, 1983; Hemelaar, 1985). In this paper, we report on the age structure, age at first reproduction, and growth rates of Rana saku aii as determined by skeletochronology. The stream frog, Rana sakuraii, is distributed in central Honshu from the Kanto to Kinki districts, Japan (Matsui and Matsui, 1990). The frogs inhabit mountain forests in summer and appear in streams in late autumn, overwintering under submerged stones. Breeding begins in February-March, and breeding activity lasts for a few weeks to a month (Kusano and Fukuyama, 1987, 1989). Specimens were collected in an upper tributary of the Bonbori River (35?42'N, 139?11'E), at 380 m, about 37 km west of the Tokyo metropolitan area. This stream is located in a mountainous region covered with planted coniferous forests of Cryptomeria japonica and Chamaecyparis obtusa and secondary deciduous forest. From 1988 to 1990, we collected breeding adults by hand during February-March. The frogs were sexed u ing secondary sexual characteristics such as thumbpad development, and snout-vent length (SVL) was measured to the nearest 0.5 mm with a slide caliper. Th fourth toe of the right or left hind leg was clipped off each frog and stored in separate vials containing 10% buffered formalin. Only the third phalanx of each toe was used for this study. Overwintering juveniles were collected from the stream during December-April. They were measured, and then some were killed in a 0.1% MS 222 solution and fixed in 10% buffered formalin to determine their

Age-related differences in cross-sectional geometry of the forearm bones in healthy women

Men exhibit age-related adaptive changes in long bone geometry, namely, endosteal resorption and periosteal apposition of bone, that help to preserve bone strength. It is not clear whether women undergo similar adaptive responses. To address this question, we assessed the bone mineral density and cross-sectional geometry of the radius and ulna at the one-third distal site by single photon absorptiometry and computed tomography (CT) in healthy young (n = 21, age 20-30 years) and older (n = 22, age 63-84 years) women. We used the CT data to compute the total subperiosteal, medullary, and cortical areas, as well as the maximum, minimum, and polar moments of inertia. We normalized the geometric parameters for bone length and performed comparisons using both the original and size-corrected data. Radial and ulnar bone mineral content and density were 20-30% lower in the older women (P < 0.0001). Ulnar width, total area, medullary area, and maximum and polar moment of inertia were greater in the older than in the younger women. Although we observed similar trends when we examined the radius data that were corrected for bone size, age-related differences in radial geometry were less pronounced and were not significant. We conclude that women undergo endosteal resorption and periosteal apposition of the ulna with age, thereby exhibiting an adaptive pattern that helps to preserve bone strength. The different behavior of these two bones suggests that local, rather than systemic, factors underlie this adaptation.

The effects of age on the response of rabbit periosteal osteoprogenitor cells to exogenous transforming growth factor-beta 2.

Additional bone and cartilage are formed if transforming growth factor-beta is injected into the periosteum of calvariae or long bones. To investigate this further, transforming growth factor-beta 2 was injected into the periosteum of the tibia of 3-day-old, 3-month-old and 2-year-old rabbits. In all instances, there was an increase in proliferation of the cells of the cambial layer of the periosteum, that is, the osteoprogenitor cells, and breakdown of the fibrous layer. Oedema was induced in the surrounding connective tissues. Over the experimental period the normal neonatal tibia is undergoing rapid growth; there is periosteal bone formation and endosteal resorption. In the experimental neonatal tibiae, an increase in periosteal bone formation is seen after three injections of 20 ng of transforming growth factor-beta 2, which is accompanied by cartilage after five injections; the amounts of induced bone and cartilage increase with the number of injections. The chondrocytes hypertrophy after 4 days and the cartilage is replaced by bone endochondrally. In contrast, after seven injections of 20 ng transforming growth factor-beta 2, there is only a small amount of new bone on the 3-month-old tibia and none on the 2-year-old tibia. One day after seven injections of 200 ng transforming growth factor-beta 2, there is a small amount of bone formation, while seven days after cartilage is found as small discrete nodules on the 3-month-old tibia, but as small areas within the bone on the 2-year-old tibia. It is concluded that the primary effect of transforming growth factor-beta 2 in this experimental model is to increase the proliferative rate of the osteoprogenitor cells in the periosteum. It is argued that transforming growth factor-beta 2 does not initiate osteoblastic or chondrocytic differentiation of osteoprogenitor cells. It is suggested that their differentiation is controlled by the local environment, in particular, the vascularity and locally circulating growth factors.