Rate Of Bone Remodeling Research Articles

Changes in the metaphysis and diaphysis of the femur proximal to the knee in rabbits with experimentally induced inflammatory arthritis.

We quantified the cross-sectional cortical bone area and remodeling rates in the ipsilateral femoral diaphysis and metaphysis of rabbits with carrageenan-induced inflammatory monarthritis of the knee. Although osteogenesis rates were significantly elevated (approximately threefold in diaphyses and sixfold in metaphyses), the cross-sectional bone area of the diaphysis was significantly diminished. Fivefold and sixfold increases in bone resorption rates were calculated in diaphyses and metaphyses, respectively. Other morphologic changes observed were porosity and net resorption of the anterior cortex and net accretion on the posteromedial cortex ("drift" of bone). These findings may have clinical significance with regard to the mechanisms and consequences of bone changes in patients with rheumatoid arthritis.

Bone demineralization, biochemical indices of bone remodeling, and estrogen replacement therapy in adults with Turner's syndrome.

The study centered on a controversy about whether long-term estrogen replacement therapy may ameliorate the osteoporosis seen in patients with Turner's syndrome. This study comprised 26 adult patients with Turner's syndrome (9 treated and 17 untreated or insufficiently treated) and 12 adult women with pure gonadal dysgenesis (8 untreated and 4 treated). A low bone density below -2 standard deviations from the age- and sex-matched predicted normal mean was documented by dual-photon absorptiometry of the lumbar spine in all the untreated and insufficiently treated patients, but only in 6 treated patients. The biochemical indices of bone resorption (urinary hydroxyproline excretion and plasma tartrate-resistant acid phosphatase activity), as well as osteoblastic function (serum osteocalcin and bone alkaline phosphatase isoenzyme), were significantly increased in untreated and insufficiently treated patients compared with treated patients. A significant negative correlation was found between biochemically documented osteoresorption and spinal bone mineral density corrected for age of the patients. Significant positive correlations were found between serum osteocalcin and bone alkaline phosphatase isoenzyme and between biochemical indices of bone resorption and formation. Although in the patients there was an evidence of a high bone remodeling rate, the rate of bone mass loss seemed to be low, comparable with that seen in oophorectomized women who had already passed their accelerated phase of bone loss. The results indicate that long-term hormonal replacement therapy is justified in gonadal dysgenesis, regardless of the karyotype of the patient, to prevent further bone mass loss.

Spontaneous release of interleukin 1 from human blood monocytes reflects bone formation in idiopathic osteoporosis.

Osteoporosis is a state of reduced skeletal mass characterized by various rates of bone remodeling. Multiple locally elaborated factors have been identified that appear to influence the cellular events in bone remodeling. The possible role(s) of these factors in the pathogenesis of osteoporosis is unknown. One such factor, interleukin 1 (IL-1), is of particular interest, as this protein is known to stimulate bone resorption and perhaps formation. Consequently, we have measured the spontaneous secretion of IL-1 activity by cultured peripheral blood monocytes obtained from 22 osteoporotic patients and 14 age-matched control subjects. Monocytes from osteoporotic patients produced more IL-1 than did monocytes from control subjects. When patients were grouped according to monocyte-produced IL-1 activity, dynamic parameters of bone formation, as judged by quantitative histomorphometric analysis of iliac crest bone biopsies and by circulating levels of bone 4-carboxyglutamic acid protein (BGP)--a marker of bone formation--were higher in subjects with elevated IL-1 activity; whereas, indices of bone resorption and static indices of bone formation were similar in subjects with either high or normal IL-1 activity. IL-1 activity released by peripheral blood monocytes appears to reflect bone formation rate in osteoporotic patients and may be of pathogenetic significance in a subset of individuals with osteoporosis.

Ovariectomy and trabecular bone remodeling in the dog.

The early effects of ovariectomy (OX) on serum biochemistry and trabecular bone remodeling in the dog were investigated. Adult beagle dams were ovariectomized (n = 8) or sham-ovariectomized (n = 6) and followed for 6 months. All dogs received an iliac crest biopsy at the time of surgery to establish baseline remodeling data. A second contralateral biopsy was obtained at sacrifice. Serum osteocalcin became significantly elevated approximately 8 weeks following OX and remained elevated for the duration of the study. Histomorphometric analysis of serial transilial specimens showed that, at 6 months, OX had significantly increased the rate of bone remodeling in the ilium. Six months following OX in the dog, changes in serum biochemistry and trabecular bone remodeling in the ilium are consistent with those seen in postmenopausal women suffering from "high remodeling osteoporosis".

Dynamic Radiologic Patterns of Paget??s Disease of Bone

Within the diaphyseal cortex, the primary resorption phase of Paget's disease is often limited either to the endosteum or to the central layers of the cortex. This results in primary resorption fronts that are usually discrete, both radiologically and scintigraphically. The subsequent activation of the subperiosteal cortex may be delayed, leading to secondary expanding fronts associated with subperiosteal new bone formation. Sequential radiographs of 19 untreated patients followed 6.4 +/- 1.2 years showed that the mean extension rate of the lesions within cortical bone was 8 +/- 0.5 mm/year per advancing front. This extension rate showed no significant change in 15 patients treated with calcitonin (CT) and/or ethane-1-hydroxy-1,1-diphosphonate (EHDP), but was significantly decreased in 14 patients treated with 3-amino-1-hydroxypropilidene-1,1-diphosphonate (APD). The increased remodeling rate of pagetic bone magnifies the radiologic changes due to mechanical, dystrophic, and metabolic interferences. Thus, a sclerotic pattern of the disease may rapidly change into a mixed or even a lytic pattern under the influence of any rarefying factor. Conversely, lytic pagetic bone may transform into dense bone through the administration of antiosteoclastic medications such as CT and APD. The reconstructive action of any new therapeutic regimen should be monitored radiologically.

Effects of Age on Cell Size and Ion Uptake in Canine Cortical Bone

In cortical bone from dogs of various ages, the uptakes of two bone-seeking isotopes, 85Sr and 99mTc-methylene diphosphonate (MDP), were compared with that of the intracellular cation 42K by using the volume of distribution (VD) technique. The rate of bone remodeling and the osteocyte volume were estimated by morphometric techniques. The percentage cell volume was related to the VD of 42K (r = 0.83; P less than 0.001) and decreased with increasing age. The decline in the VD of 85Sr and 99mTc-MDP with aging was related to the decrease in bone formation (r = 0.90; P less than 0.001). On a logarithmic plot, the cell volume and the VD of 42K had a linear relationship with the rate of new bone formation, the VD of 85Sr, and the VD of 99mTc-MDP. Our results demonstrate that, with increasing age in dogs, the bone formation rate and cell size decrease, as does the uptake of 42K, 99mTc-MDP, and 85Sr.

Oophorectomy and cortical bone remodeling in the beagle.

Cortical bone remodeling measurements were carried out on the ribs of 6 spayed and five control Beagle dams which had been subjected to a period of observation equal to more than one sigma of cortical bone remodeling activity. The results of the measurements of static and dynamic parameters indicate that the lack of ovarian hormones does not produce a major alteration in the rates of cortical bone remodeling, but does result in an increase in the number of resorption spaces per mm2 of cortical bone without altering the parameters of bone function. This latter fact supports the hypothesis that decreased levels of circulatory ovarian hormones may influence the duration of the resorption activity as well as possibly uncoupling the resorption/formation (R/F) mechanism of the bone remodeling unit.

228 Th Retention and Dosimetry in Beagles

Total-body and skeletal retention of 228Th were determined in a group of 104 young adult male and female beagles for about the first 7 years after the injection of 0.00159 to 2.76 muCi/kg. Ratios of 224Ra / 228Th , 212Pb / 228Th , and 212Bi / 228Th in the skeleton and in soft tissues of 20 beagles were measured as a function of time after injection. A humerus, femur, and ulna from 20 dogs dying 7 to 554 days after injection were sectioned, and the 228Th concentration was obtained for each piece. Percentage biological retention in the skeleton of 228Th at t days after injection could be described as 68.1 e-0. 000180t . Ratios of daughter-to-parent activity in soft tissue showed no definite trend with dose level or time and averaged Ra/Th = 0.56, Pb/Th = 0.83, and Bi/Th = 0.91, whereas the ratios for the skeleton varied with both dose level and time. Ratios of activity in the skeleton from lowest to highest dose level after 2 years following injection ranged between Ra/Th = 0.88 to 0.95, Pb/Th = 0.78 to 0.92, and Bi/Th = 0.77 to 0.90. Retained 228Th was deposited most heavily in parts of the skeleton with much trabecular bone, much bone surface area, and high bone remodeling rates. No changes in this deposition pattern could be discerned during the 554 days over which the measurements of sectioned long bones were made.

Postmenopausal osteoporosis: A heterogeneous disorder as assessed by histomorphometric analysis of iliac crest bone from untreated patients

Twenty-six women with untreated postmenopausal osteoporosis underwent iliac crest biopsy following tetracycline-labeling and mineral metabolism studies. Histomorphometric assessment of their bone remodeling rates, including formation determined by the tetracycline-labeling technique, revealed considerable variation. Eight women had no evidence of active bone formation (inactive remodeling osteoporosis), whereas the others showed a spectrum of bone formation rates (active remodeling osteoporosis). Clinical and biochemical studies failed to predict the histomorphometric findings. Postmenopausal osteoporosis is a histologically heterogeneous disorder with morphologic expression in bone that cannot be predicted by single or combined routine clinical and laboratory parameters. Bone biopsy, necessary to identify the histologic lesion and assess skeletal dynamics, may prove to be important for optimal therapy of osteoporosis, as a variety of agents—with different effects on bone remodeling—are available.

The effects of trienbolone acetate on carcass composition, conformation and skeletal growth of turkeys.

1. The carcasses of 66- and 73-d-old stag turkeys implanted with 20 mg trienbolone acetate (TA) at 49 d of age were analysed and the results compared with those of untreated controls. 2. Treatment with TA improved growth, increased carcass moisture and tended to decrease carcass fat and ash; protein content was not altered by implantation. 3. Treatment with TA produced a marked improvement in efficiency of conversion of dietary protein to carcass protein. 4. Carcass formation of 70- and 77-d-old turkeys of both sexes implanted with 20 mg TA at 49 d of age was not markedly different from that of controls in terms of the relative proportions of the major body components nor in relative skeletal proportions. 5. Implantation with TA reduced linear and appositional skeletal growth both relative to soft tissue growth and relative to skeletal growth of control turkeys. 6. The rate of bone remodelling was reduced more than the rate of appositional growth so that bone cortical thickness was increased. 7. The changes in the skeleton effected by TA are consistent with the hypothesis that the drug acts by decreasing the rate of protein turnover, with catabolism being depressed more than anabolism.

Quantification of bone stresses during remodeling

An experiment to quantitate the effect of compressive stress upon bone remodeling rate was devised. Remodeling herein is described as the renewal process of bone separate from initial formation. A finite element mathematical model of the rabbit calvarium was devised. Actual rabbit calvaria were stressed utilizing a load cell monitored lever type loading device. They were periodically stained with fluorescing bone seeking dyes. Upon necropsy, histologic sections were prepared and the growth rate at known locations in the stressed area was measured by planimetry. Observed bone formation was subdivided into lamellar and fibrous. Lamellar bone formation (remodeling) rate remained above control levels until stresses of approximately 360 psi were reached; above this level remodeling rate fell to or below control. Fibrous bone exhibited higher formation rates which decreased with increasing stress but remained above control. At stresses approaching 1000 psi the technique could not measure formation rates due to the confused fibrous bone formation.

A Model For Clinical Research Studies of Renal Osteodystrophy in Children

Renal osteodystrophy in children differs from that seen r in the adult population in several important ways. First, it is a more frequent complication of chronic renal failure in children,^1,2which is probably a result of the more rapid rates of bone remodeling and renewal. Second, it is also one of the most important contributing factors in linear growth failure. Third, the underlying cause of renal failure is a critical factor in determining the timing of onset and specific type of renal osteodystrophy in children. A recent report from one large center will serve to emphasize this point.³Hereditary nephropathies, renal hypoplasia, and malformations of the urinary tract with or without infection predominate under the age of 3 years, when growth potential is greatest. The interval between onset of renal insufficiency and terminal renal failure varies widely (mean = 2.5 to 6.3 years) but tends to be longer in

Effect of hypophysectomy on dentin production in maxillary incisors in the rat

abstract— The effect of hypophysectomy on the dentin production and on the longitudinal growth of the maxillary incisors of female rats 60–105 d of age was determined In‐ the tetracycltne technique. In normal rats, the highest rate of dentin apposition amounted to about 23μm per clay in the middle part of the tooth with lower values in apical and incisal directions. Because of incisal attrition, the tooth was exchanged in about 55 d, corresponding to a longitudinal growth rate of'about 400μm per day. After hypophysectomy, the rate of dentin production was reduced to about 60%, with a considerable variation depending on the position of the odontoblasts along the tooth. The longitudinal growth rate was reduced to about 50% of normal. As the length of the tooth was the same within the period studied, this resulted in a slower transfer of the odontoblasts along the tooth and a time delay of about 55 d before they reached the incisal part of the tooth. The total dentin production of the odontoblasts in the hypophysectomized animals was the same as in normals. Compared with the effect of hypophysectomy on the rate of longitudinal bone growth and cortical bone remodeling, the effect on the dentin production and longitudinal growth of the incisors is less pronounced, indicating differences in sensitivity to hormones between the different cell systems.

A Theory of the Induction of Bone Cancer by Alpha Radiation

A theory of the induction of osteosarcoma by α particles fits the data for radium in man and dog over the entire dose-time-response surface. The theory postulates that an endosteal cell near bone surface is transformed by three events. Two initiation events, each with a probability of $4\times 10^{-8}/\text{rad}$ (an effective target diameter of 100 A), are produced in a single cell by two α particles. A promotion event then occurs at a rate of $10^{-2}/\text{year}$, not related to radiation, but proportional to the rate of bone remodeling. In competition with these events is the killing of any endosteal cell by an α particle with a probability of $10^{-2}/\text{rad}$. Killed endosteal cells are assumed to be replaced by stem cells at a rate of $10^{-1}/\text{day}$. Postulated tumor growth takes 3-6 years. These values for man are preliminary. The probability per rad per cell of each initiation appears to be ∼10 times larger in dog than in man. A new method of three-dimensional analysis provides a compact...

Retention and Skeletal Dosimetry of Injected 226 Ra, 228 Ra, and 90 Sr in Beagles

Total-body retention has been determined by in vivo counting in beagles injected with 226Ra (125 dogs), or 228Ra (78 dogs), or 90Sr (96 dogs). The radionuclides were administered intravenously in a citrate buffer solution when the animals were about 1.4 years of age. Retention measurements now extend to more than 14 years after injection; therefore, future revision of these retention equations appears unlikely since the median lifespan in our control beagles is about 12.7 years. Dogs injected with about 10 Ci 22Ra/kg had a higher long-term retention than those receiving 0.04 to about 4 MCi 226Ra/kg. This has been interpreted as a consequence of radiation damage to the bone remodeling processes at high 226Ra concentrations. Totalbody biological retention ER (%)] at t days could be described by the following functions. 226Ra, for 1400 days after the injection of 10 /ACi/kg: R(%) = 41e-0.56t + 10e-.O73t + 20e-0-0049t + 29e-0.00030t, 226Ra, for 5200 days after the injection of 0.04 to 4 MCi/kg: R(%) = 25e-098t + 21e-0.27t + 21e-0.016t + 18e-0.0020t + 15e-0.0001St, 90Sr for 5000 days after injection: R(%) = 36e-o.95t + 29e-0.12t + 10e-0.0091t + 12e-o.-0o9t + 13e-.0001t. The 228Ra retention data were not analyzed numerically, but visual inspection of the curves prepared for individual dogs indicated that retention could be described adequately by the retention equation derived for dogs given 0.04 to 4 ACi 226Ra/kg. The average skeletal radiation dose rate and cumulative radiation dose were calculated for each beagle injected with 22Ra or 22SRa or 90Sr using the appropriate retention equation, normalized to each dog's individual retention measurements. Allowance was made in the 226Ra calculations for the changing skeletal retention of 222Rn and its radioactive daughters; in the 228Ra calculations for the diminution of 228Ra activity by radioactive decay as well as for the ingrowth and skeletal retention of 228Th and its radioactive daughters; and in the 90Sr calculations for the diminution of 90Sr concentration by radioactive decay and the escape of #-energy from bone. The half-time (4621 days) of the longestlived component in the 9Sr retention equation was similar to that for the lower-level Ra dogs. This may reflect the net remodeling rate of cortical bone in the beagle skeleton.

Comparison of Stainless Steel and Composite Plates in the Healing of Diaphyseal Osteotomies of the Dog Radius: Report on a Short Term Study

The rigid fixation of fractures is generally accepted as the best method to achieve union when open treatment of a fracture is undertaken. This has led to the development of plates that have a greater overall dimension and stiffness compared to earlier plate models, as exemplified by the Lane or Eggers type of plate. In our experience the more rigid plate generally leads to satisfactory union, but also carries with it the risk of refracture, either through a screw hole or across the original fracture after plate removal. Experiments by Uhtoff and Dubuc on experimental animals showed that plate induced osteopenia existed when a rigid plate was applied to an intact or osteomized canine femur. These results provide a possible explanation for the occurrence of late fracture. The study to be described is based on the hypothesis that a rigid plate applied to bone induced localized immobilization osteopenia, which ultimately weakens the bone and leads to the development of late fracture. The study was designed to compare a plate made of stainless steel, which exhibited mechanical stiffness comparable to that of devices presently in use, with a plate made of a composite material, which exhibited decreased stiffness by nearly one order of magnitude. It had been demonstrated by engineering analysis that the less stiff plate would allow the bone to experience normal loading, and it was thought that this loading would modulate the rate and pattern of bone remodeling, thereby resulting in bone of greater strength and size as compared to a more rigidly plated bone.

Osteomyelitis of both femora in a patient on maintenance hemodialysis with severe uremic osteopathy.

The case is reported of a 29 y. old woman with chronic renal failure and severe azotemic osteopathy treated by maintenance hemodialysis. At autopsy bilateral symmetrical osteomyelitis of the medial corticalis of both femoral diaphyses was found. Osteomyelitis was associated with large, partially penetrating cortical sequesters, and the formation of involucra and cloaca. The coincidence of azotemic osteopathy with osteomyelitis in patients kept on maintenance hemodialysis has not been reported so far. An increased rate of bone remodelling and an enhanced skeletal blood flow as a consequence of uremic metabolic bone disease is thought to raise the risk of hematogenous osteomyelitis. The symmetrical localization in both femora may be due to a local increase of bone remodelling where the riders muscles insert (caused by an altered tonus of riders muscles in uremic myopathy) or in stress zones from bending stress of the femora.

Aspects of parathyroid physiology in mammals.

This report summarizes the parameters of parathyroid physiology in the mammal. Emphasis is given to the part played by this hormone in the processes of growth and remodelling in bone as well as to its function in the maintenance of a relatively constant level of ionic calcium in the extracellular fluid. The importance of phosphate ions has been shown, particularly with respect to their role in the rate of Ca-transport through the extracellular fluid compartments, and their influence on the rate of parathyroid secretion. In addition, the inter-relationship of the newly discovered hormone, thyrocalcitonin, is considered. The latter hormone, by suppressing resorption of bone, may have an influence in stabilizing plasma levels of calcium; it also has a moderate, but long range effect on the rate of bone remodelling. Finally, an attempt has been made to relate the vast amount of work done with these two hormones in mammals to their phylogenetic development in vertebrates. It is suggested that the parathyroids developed at the time when the specialization of bone in vertebrates produced a solid structure which was incompatible with the fluid calcium concentration needed for the maintenance of many physiological functions. The parathyroid hormone, by its action to increase the transfer of calcium from bone against a concentration gradient, permitted these vertebrates to maintain the higher fluid calcium ion concentration needed for the normal functioning of the animal.

Ability of 47Ca kinetic analysis to discriminate metabolic states affecting bone formation in dogs

This study was designed to investigate rates of bone remodeling by simultaneous determinations of two parameters that are somewhat independent reflections of the remodeling process. One of the parameters, the F ratio, is defined as the ratio of the length of internal surface at which bone formation is active (assessed by microradiography and confirmed by tetracycline labeling) to the total length of internal surface in bone sections from biopsy sites. The second is an empiric parameter, A (as defined by Bauer), and calculations are based on measurements of radioactivity in plasma at various times after intravenous injection of 47Ca and on the amount of radiocalcium excreted during the same period. One or the other of these parameters has been studied previously by this group and by other investigators, but we can find no reported attempt to perform these two specific measurements simultaneously in the same group of adult animals. Three groups of dogs differing in their hormonal balance and, hence, in their overall rates of bone remodeling were studied. The results showed that among the three groups there was comparatively little overlap in the ranges of A values, of local F ratios measured in the rib (F rib), or of local F ratios measured in the femur (F femur). It was also noted that, within any one of the group, A values, F rib ratios, and F femur ratios were not correlated. It was further shown that knowledge of both A and F values can provide better discrimination among these three groups than could be achieved with either parameter alone.

Strontium-90 and skeletal formation.

The potential radiostrontium level to be expected in the skeletons of growing children as a result of environmental contamination was computed. Results are based on available data on the rate of bone remodeling and exchange, the rate of skeletal growth, and the level of /sup 90/Sr in the biosphere.