Periosteal Apposition Research Articles

Genetic effects on bone mass and turnover-relevance to black/white differences.

The mass of a bone is given by its volume and its apparent density—mass per unit external volume. Most measurements of so-called density are of mass incompletely normalized by some index of bone size. Genes control about 60% to 75% of the variance of peak bone mass/density and a much smaller proportion of the variance in rate of loss. Genetic influence on bone mass/density are mediated in large part by body size, bone size, and muscle mass. Most of the fifty-fold increase in bone mass from birth to maturity is due to bone growth, which is linked to muscle growth and bodily growth. Three-D apparent bone density in the vertebrae increases about 15% during the pubertal growth spurt. The genetic potential for bone accumulation can be frustrated by insufficient calcium intake, disruption of the calendar of puberty and inadequate physical activity. The growing skeleton is much more responsive than the mature skeleton to the osteotrophic effect of exercise, which is mediated by the detection of deviations from a target value for strain, and orchestration of cellular responses that restore the target value, processes collectively termed the mechanostat. Production of metaphyseal cancellous bone and growth in length are both linked to endochondral ossification, which is driven by growth plate cartilage cell proliferation. Production of diaphyseal cortical bone and growth in width are both linked to periosteal apposition, which is driven by osteoblast precursor proliferation. During adolescence trabeculae and cortices become thicker by net endosteal apposition, which increases apparent density. Two lines of evidence support a genetic basis for black/white differences in bone mass. First, the magnitude (10% to 40%) is incommensurate with known nongenetic factors. Second, the difference is already evident in the fetus and increases progressively during growth, especially in adolescence; the difference in peak bone mass persists throughout life. The genetic determination of bone mass is mediated by two classes of gene. The first regulates growth of the body, including muscles and bones, under the control of a master gene or set of genes whose products function as the sizostat. The second regulates the increase in apparent bone density in response to load bearing, under the control of a master gene or set of genes whose products function as the mechanostat.

Inhibition of bone resorption by pamidronate cannot restore normal gain in cortical bone mass and strength in tail-suspended rapidly growing rats.

To clarify how the changes in bone formation and resorption affect bone volume and strength after mechanical unloading, the effect of inhibition of bone resorption by a potent bisphosphonate, pamidronate, on bone mineral density (BMD), histology, and strength of hind limb bones was examined using tail-suspended growing rats. Tail suspension for 14 days reduced the gain in the BMD of the femur at both the metaphysis rich in trabecular bone and the diaphysis rich in cortical bone. Treatment with pamidronate increased the total BMD as well as that of the metaphysis of the femur but had almost no effect on the BMD of the diaphysis in both control and tail-suspended rats. Histological examinations revealed that 14-day tail suspension caused a loss of secondary cancellous bone with a reduction in the trabecular number and thickness in comparison with control rats. In the femoral diaphysis, the diameter and cortical bone thickness increased to a lesser degree in tail-suspended rats when compared with rats without tail suspension, and a marked reduction in bone formation and the layers of alkaline phosphatase-positive cells was observed at the periosteal side. Pamidronate treatment increased secondary cancellous bone but could not restore normal growth-induced periosteal bone apposition and bone strength. Because the material strength of the femoral diaphysis at the tissue level was not affected by pamidronate treatment, the inability of pamidronate to prevent the reduction in physical strength of the femoral diaphysis does not appear to be due to a change in the quality of newly formed bone. These results demonstrate that tail suspension reduces the growth-induced periosteal modelling drift and that the antiresorptive agent pamidronate is unable to restore normal periosteal bone apposition.

Effects of vigorous exercise training and beta-agonist administration on bone response to hindlimb suspension.

The effectiveness of dobutamine (Dob) in preventing bone loss during 14 days of hindlimb suspension (Sus) was tested in exercise-trained (Ex; n = 25) and sedentary (Sed; n = 22) rats (age 155 days). One-half of each group was given Dob (2 mg . kg-1 . day-1) or saline (Sal). Histomorphometric measurements at midfemur revealed a 17% smaller cortical bone area (CBA) and a 32% lower periosteal mineral apposition rate (MAR) in suspended vs. nonsuspended Sed/Sal rats. Dob abolished this decline in CBA in Sed/Sus rats, probably via an attenuation of the decrease in periosteal MAR; similar but nonsignificant effects on cross-sectional moment of inertia were observed. Nonsuspended Ex rats had no change in bone CBA when CBA is indexed to body weight. Sus appeared to uncouple the relationship between soleus weight and CBA. Dob attenuated the 43% decline in soleus weight after Sus in Ex but not in Sed rats. In summary, vigorous Ex before Sus does not affect loss of bone mass due to unloading; Dob effectively maintains CBA in Sed rats subjected to suspension.

Orthodontische Zahnbewegung in Richtung auf unverheilte und verheilte Extraktionsbereiche

The aim of this experimental study was to assess the advantages of an early or delayed treatment start after tooth extraction on the basis of hard-tissue findings (density, maturity, osteodynamics) and of soft-tissue responses at the extraction site. Following bilateral extraction of the second incisors, reciprocal space closure was initiated in 3 foxhounds (age: 3.5 years): group 1 (6 teeth) 12 weeks after extraction, group 2 (6 teeth) immediately after extraction. After an 8-week bodily tooth movement period and a 2-month retention period, evaluation was undertaken on the basis of clinical/radiologic and histologic criteria (sequential polychromatic bone marking, light microscopy). Histologic analysis yielded the following findings in group 1 (delayed tooth movement): low bone density at the extraction site with more mature lamellar bone, pronounced horizontal atrophy of the alveolar process with periosteal bone apposition in direction of tooth movement, increased tendency towards gingival invagination. The findings in group 2 were characterized by: higher bone density with less maturity (bundle bone) at the extraction site, broader alveolar process, reduced tendency towards gingival invagination. No qualitative difference between the 2 groups was found with respect to root resorption. The histologic findings therefore indicate that orthodontic retraction into extraction sites should be initiated at an early stage.

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.

Effect of ovariectomy upon weaning on the morphometric parameters of femorae and tibiae of growing rats.

To assess the effects of early ovariectomy on whole bone density and several morphometric and serum markers of bone metabolism, female Wistar rats were ovariectomized or sham-operated upon weaning. The animals were fed ad libitum. After 8 weeks, the increase in the weight gains of ovariectomized rats was minute when compared with the control animals. The whole bone densities of the femorae of ovariectomized rats were slightly reduced when compared with the sham-operated animals. The proximal cross section of the femorae of the ovariectomized rats exhibited enhanced periosteal bone apposition and increased cortical area when compared with the sham-operated animals, but the differences were not statistically significant. The cancellous bone of the femora and the proportional areas of trabeculae of the proximal tibia were reduced in ovariectomized rats. It is concluded that ovariectomy upon weaning caused a clear tendency toward osteopenia. Cancellous bone was clearly affected after ovariectomy, indicating its relation to gonadal hormone regulation even during growth.

Short-term effects of high dose estrogen on tibiae of growing male rats.

The short-term effects of estrogen at a single high dose (4 mg/kg body weight/day for 14 days) were determined on tibiae in the normal (noncastrate) growing male rat. In cortical periosteal bone, at a middiaphyseal site devoid of resorbing activity, estrogen suppressed periosteal bone formation and apposition rates, resulting in a smaller cross-sectional area. In middiaphyseal endocortical bone, estrogen had no effect on apposition and formation rates and, because medullary area was unchanged, probably had no effect on endocortical bone resorption. In the proximal tibial metaphysis, estrogen greatly suppressed longitudinal growth rate. In a site within the metaphysis adjusted for the effects of growth, cancellous mineral apposition was greatly reduced by the hormone. Estrogen-treated rats retained more of a fluorochrome label deposited in cancellous bone at the beginning of the study than vehicle-treated animals, indicating a reduced net bone loss. As a result of the lowered resorption induced by estrogen, cancellous bone mass (area and perimeter) were both significantly higher in estrogen-treated rats. No evidence was found for an anabolic action of the hormone in the male rat; indeed, estrogen reduced indices of bone formation.

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.

Electrical stimulation of leg muscles increases tibial trabecular bone formation in unloaded rats.

Rat head-down hindlimb suspension (HS) has been shown to induce hindlimb cancellous bone loss. As HS is known to associate unloading with progressive disappearance of hindlimb muscle contractions, we investigated whether persisting muscle motion could modify suspension-induced bone disorders or even prevent them. Chronic electrical stimulation (ES) was applied to leg muscles of rats during 3-wk hindlimb suspension, the lack of support for hindlimbs maintaining a hypodynamic situation. The histomorphometric characteristics of the proximal tibial metaphysis were analyzed. At the end of this protocol of combined suspension and stimulation, trabecular bone loss remained similar to that of nonstimulated HS animals. However, trabecular bone cell activity parameters showed greater bone formation after muscle stimulation in unloaded animals, with significantly increased osteoblastic, osteoid, and mineralizing surfaces. In addition, periosteal mineral apposition rate and cancellous bone formation rate, markedly decreased by suspension, were not significantly different in suspended stimulated compared with normal loaded animals. This enhanced formation activity could be related to persistence of muscle activity, as shown by partial preservation of muscle mass. However, direct electrical effects on bone cannot be excluded. Thus, despite muscle stimulation, with enhanced bone formation, isolated suppression of hypokinesia has not been able to counteract bone effects of unloading. This finding supports the hypothesis of the importance of mechanical loading to maintain bone architecture.

Pachydermoperiostosis: Dermatological, neurological and radiological observations

A case of pachydermoperiostosis is described. Interesting features were the presence of carpal and tarsal tunnel syndromes, chronic leg ulcerations and large calcification of the Achilles tendon. Neurological alterations were explained by the stenosis of the tunnels secondary to the periosteal apposition. Chronic leg ulcerations were probably due to neurological and circulatory alterations.

Monarticular Erosive Osteoarthritis

Although monarticular erosive osteoarthritis is uncommon, it is not rare. In our example, there was a monarticular presentation of cartilage destruction, soft tissue swelling, and linear periosteal bone apposition. Such bone apposition adjacent to affected joints is not uncommon in erosive osteoarthritis. However, when observed in the context of monarticular disease, particularly when accompanied by soft tissue swelling, it could easily be mistaken for an infectious arthritis.

The "mirror image" and "two-thirds" types of hemispherical spondylosclerosis.

Clinical and radiological examination of 167 hemispherical spondylosclerosis (HSS) patients (56 male, 111 female) revealed a total of 186 cases of HSS with multiple incidences occurring in 18 patients. Radiologically these HSS cases were characterized by erosion and new bone formation at the inferior and upper end plate of the vertebra below, periosteal bone apposition or ossification of the anterior longitudinal ligament, spondylophytes, and signs of degenerative alteration of the vertebra and disc. In addition, the size and location (anterior, middle, posterior third) of each HSS in the lateral view was investigated. The cases were also investigated for reflection phenomenon between supra- and infradiscal sclerosis and for kyphotic angulation of the two adjacent vertebrae. The results showed that in 105 cases (56.5%) the HSS filled out the entire vertebral area; 97 cases (52.2%) showed a mirror-image type HSS; while in 8 cases (4.3%), the infradiscal sclerosis was polymorphic. In 81 cases (43.5%), the sclerosis was limited to the anterior two-thirds; this is termed "two-thirds" type. All 81 of these cases of HSS showed a kyphotic angulation of at least 4 degrees. Of these, 61 (32.8% of the total) showed reflection phenomenon while 20 (10.7% of the total) had polymorphic infradiscal sclerosis. Overall, 158 cases of HSS (85%) exhibited the reflection phenomenon between supra- and infradiscal sclerosis, whereas 28 cases (15%) revealed polymorphic sclerosis of the subadjacent vertebra. Kyphotic angulation was completely absent when HSS was visible in the entire vertebra. A dorsal gap of the disc space was seen in 36 cases (19.4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of basic fibroblast growth factor (bFGF) on bone formation in growing rats

The effects of basic f broblast growth factor (bFGF) administered intravenously at dosages of 0.1 and 0.3 mg/kg per day for 7 days to growing rats are reported. Static and dynamic histomorphometry techniques were applied to the microradiographs and undecalcifed ground sections of the proximal tibiae and tibial shafts. The bone histomorphometric analyses in the proximal tibia revealed that 0.1 mg/kg per day of bFGF increased longitudinal growth rate, cartilage cell production rate, and metaphyseal bone area. In the tibial shaft, the endocortical mineral apposition and bone formation rates, total bone area, total osteoid area, and medullary bone area were increased, but the periosteal mineral apposition and bone formation rates were depressed. Two weeks after the cessation of treatment, the increased osteoid bone on the endocortical surface and in the marrow cavity was completely calcified, and the total mineralized area in the tibial shaft was significantly increased. The rats given 0.3 mg of bFGF/kg per day showed retarded weight gain, defective calcification at the growth plate metaphyseal junction, and on the endocortical surface. The growth plate width was increased, and the longitudinal growth rate, cartilage cell production rate, endocortical labeled surface, and bone formation rate were decreased. Two weeks after the cessation of treatment, these changes were almost reversed, and the longitudinal growth rate and cartilage cell production rate were increased as rebound phenomena. These results suggest that a low dose (0.1 mg/kg per day) of bFGF stimulates endosteal and endochondral bone formation and depresses periosteal bone formation in growing rats.

Osteopenia in rats supported by intravenous nutrition

The etiology of bone disease seen in long-term total parenteral nutrition patients is poorly defined. This study examined the question of whether abnormal bone could be induced in otherwise normal weanling rats fed a balanced nutrient solution intravenously. Young adult, male Wag/Rij rats were divided into three groups. One group was fed a commercial liquid research diet, one group received an indwelling jugular catheter and was fed an intravenous elemental solution formulated to be nutritionally complete, and one group received an indwelling catheter but was fed the commercial liquid diet orally. Significant differences were seen between groups in percent bone, femur length, growth-plate width, endosteal label area, periosteal mineral apposition rate, and periosteal and endosteal bone-formation rates. This study suggests that intravenous administration of otherwise adequate nutrients to rats results in altered bone remodeling compared to orally fed cohorts.

The two faces of growth: benefits and risks to bone integrity.

Bones grow by two processes: cortical bone is made by periosteal apposition (growth in width), and cancellous bone is made by endochondral ossification (growth in length). In both the axial and appendicular skeleton, about half of peak adult bone mass is accumulated during the adolescent growth spurt, which occurs two years earlier in girls than in boys, and is under pituitary control via interactions between growth hormone and sex hormones. Throughout growth, but particularly during adolescence, the ability of bone to adapt to mechanical loading is much greater than after maturity. This is the main reason why the effects of physical activity on bone are greater in cross-sectional studies in young athletes than in longitudinal studies in previously sedentary adults. In wild animals, by the time growth has ceased, the bones must be as strong as they will ever need to be, and attainment of further strength after cessation of growth would serve no biologic purpose. Adaptation of growing bone to mechanical loading is the purpose of the mechanostat, which enables physiologic adaptation in individuals to establish and maintain a species-specific property of the bones that is determined by evolutionary adaptation in populations. But growth confers risks as well as benefits to the skeleton. The large increase in incidence of upper extremity (particularly lower forearm) fractures, coincident with the adolescent growth spurt in both sexes, is due to an increase in cortical porosity as a consequence of an increase in intracortical bone turnover, which supplies some of the calcium needed by the growing ends of the long bones. This enables an increased demand for calcium to be spread over a longer time, analogous to the cyclic physiologic osteoporosis which occurs during the antler growth cycle in deer. The subsequent decline in cortical porosity is responsible for the continued increase in radial bone density after cessation of growth, referred to as consolidation. In the present state of knowledge, an increased incidence of fracture during the adolescent growth spurt is the inescapable consequence of an appropriate level of physical activity, and is the price that has to be paid in order to maximize bone accumulation during growth and minimize fracture risk in old age.

Myelofibrosis associated with prominent periosteal bone apposition report of two cases

Myelofibrosis is a myeloproliferative disorder that is characterized by splenomegaly and bone marrow replacement by fibrous tissue. The predominant radiographic feature is osteosclerosis; however, in rare instances, periosteal bone apposition or periostitis is apparent in the metaphysis of the distal femura and proximal tibiae. It has been suggested that periostitis, when associated with fever and bone pain, is indicative of more aggressive disease. We report this unusual radiographic finding and its similar appearance to hypertrophic osteoarthropathy in two patients with myelofibrosis. In our patients, the presence of periosteal bone apposition did not correlate with increased disease aggressiveness.

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.

Variation of cortical hypertrophy depending on the medullary filling material: An experimental study of canine tibial diaphysis

In order to evaluate the mineralization of bone after polymethyl methacrylate cementation, measurements of the periosteal apposition were made histologically and measurements of the bone—mineral content were made by dual-photon absorptiometry of the tibial diaphysis in 15 adult mongrel dogs in paired studies. Six dogs were investigated 4 weeks after intramedullary reaming of both sides and obturation of the medullary cavity with bone—wax on one side. Nine dogs were reamed on both sides. The medullary cavities were filled with polymethyl methacrylate bone—cement and bone—wax, respectively. The authors found (1) an increased bone—mineral content and an increased periosteal apposition after filling with bone—wax in comparison with the reamed side and (2) a decreased bone—mineral content and a decreased periosteal apposition on the cemented side in comparison with bone—wax. These findings are interpreted as consequential upon repair processes with a high remodeling and mineralization rate after reaming or filling with bone—wax, whereas remodeling is inhibited after filling with acrylic bone—cement.

Variation of cortical hypertrophy depending on the medullary filling materialAn experimental study of canine tibial diaphysis

In order to evaluate the mineralization of bone after polymethyl methacrylate cementation, measurements of the periosteal apposition were made histologically and measurements of the bone—mineral content were made by dual-photon absorptiometry of the tibial diaphysis in 15 adult mongrel dogs in paired studies. Six dogs were investigated 4 weeks after intramedullary reaming of both sides and obturation of the medullary cavity with bone—wax on one side. Nine dogs were reamed on both sides. The medullary cavities were filled with polymethyl methacrylate bone—cement and bone—wax, respectively. The authors found (1) an increased bone—mineral content and an increased periosteal apposition after filling with bone—wax in comparison with the reamed side and (2) a decreased bone—mineral content and a decreased periosteal apposition on the cemented side in comparison with bone—wax. These findings are interpreted as consequential upon repair processes with a high remodeling and mineralization rate after reaming or filling with bone—wax, whereas remodeling is inhibited after filling with acrylic bone—cement.

Does weight-bearing exercise affect non-weight-bearing bone?

It was previously reported that weight-bearing exercise increases femur periosteal formation in 3-year-old, 230 kg cross-bred sows. To determine if this weight-bearing exercise also stimulated non-weight-bearing bone, bone formation in the seventh rib from these same sows was measured histomorphometrically on the periosteal, endocortical, and osteonal envelopes. The sows were randomly assigned by body weight to basal (B, n = 6), control (C, n = 7), or trained (T, n = 7) groups. After 3 weeks of exercise adaptation, T walked on a treadmill for 17 weeks at 5 km/h, 20 minutes/day, 5 days/week, at 5% grade. Groups were sacrificed initially (B) or after 20 weeks (C and T). Periosteal mineral apposition rate (MAR) was calculated over 136 days. Osteonal and endocortical MAR were calculated over the 14 days prior to sacrifice. There were no effects of exercise on the periosteal or endocortical percentage double-labeled surface (dLS/BS), osteonal remodeling frequency (N.dL.On/B.Ar), or MAR in any bone envelope of the rib. In conclusion, weight-bearing exercise sufficient to stimulate periosteal formation in the femur did not activate formation in the rib. Bone response to weight-bearing exercise appears to be specific to the loaded bones.