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PubMed1991

Regional blood flow and strontium-85 incorporation rate in the rat hindlimb skeleton.

Regional distribution of radioactive microspheres and 85Sr incorporation rate in the os ilium, femur, and tibia were determined in 44 rats. In 15 additional animals, regional blood flow was measured with the reference sample technique. Highest numbers of microspheres were found in the distal femoral and proximal tibial metaphyses. Highest blood flow rates were found in the os ilium, the caput femoris, and distal femoral and proximal tibial metaphyses. The diaphyses and epiphyses of the femur and tibia had a relatively lower perfusion. The regional 85Sr incorporation rate was correlated (r = 0.67) to the regional distribution of the microspheres. The dispersion of the data was large and this was mainly due to biological variation. The results describe the regional distribution of blood flow in the rat hindlimb and demonstrate a close association between blood flow and mineral turnover in normal rat skeletal tissue as shown by the correlation between microsphere and 85Sr incorporation rate distribution.

Animals↗
PubMed1992

Rabbit knee immobilization: bone remodeling precedes cartilage degradation.

This study analyzed processes underlying osteoporosis and osteoarthrosis after short-term immobilization of the right hind limb of postadolescent (2.8 kg) and mature (4.0 kg) rabbits. After 3 weeks, the lateral posterior aspect of the lateral tibial plateau and the lateral femoral condyle of the immobilized limb exhibited prominent subchondral vascular eruptions. Femoral metaphyseal bone density decreased 27 and 18% in the immobilized limbs of postadolescent and mature rabbits, respectively. Calcein green fluorescence increased 1.9-fold (p less than 0.001) in the metaphyseal trabeculae of immobilized femurs. With immobilization, sulfate incorporation into femoral cartilage glycosaminoglycan increased, although total cartilage glycosaminoglycan and hydroxyproline levels were unchanged. Thymidine incorporation into DNA increased four- to fivefold in tibial and femoral cartilage of the immobilized limb. In this study, bone loss and remodeling preceded erosive cartilage degradation.

Animals↗
PubMed1994

Cortical and trabecular bone contribute strength to the osteopenic distal radius.

Fractures of the distal radius are common, especially in postmenopausal women, and their prevalence increases with age. Knowledge of the factors that increase the risk of fracture in this metaphyseal region would have predictive and therapeutic implications. Of particular interest in this study were (a) the relative contributions of cortical and trabecular bone to the strength of the distal radius and (b) the best radiographic features to use as strength indicators. In 21 forearms from fresh cadavera (median age at the time of death, 75 years), single photon absorptiometry and quantitative computed tomography were used to determine bone mineral content (BMC), density (BMC/W), and cross-sectional properties of the radius at distal and midshaft sites. Mechanical testing of the forearms then was used to determine the ultimate force and energy to cause the type of fracture that might be caused by a fall on the outstretched hand. Twelve of the 17 tested specimens sustained a fracture of the distal radius, and five sustained a fracture of the scaphoid. In the group of fractures of the distal radius, we found the cross-sectional area and moment of inertia of the cortical shell at the metaphyseal site to be better correlates of strength than the trabecular area and trabecular moment. In contrast, strength correlated much better with trabecular density than with cortical density. Overall, the best correlates of strength were the BMC and BMC/W at either the distal or proximal site. On balance, these results suggest that the thin cortical shell contributes substantially more to the mechanical strength of the distal radius than has been commonly appreciated.

Aged↗
PubMed2000

Changes in cross-sectional geometry of the distal femoral metaphysis associated with inflammatory arthritis are reduced by a bisphosphonate (zoledronate).

An increased risk of fracture is a feature of rheumatoid arthritis and of animal models of inflammatory arthritis. We examined geometrical changes in the metaphyseal cortex of the distal femur in an animal model of inflammatory arthritis. Additionally, we examined the effect of a bisphosphonate in preventing these changes. Five groups of rabbits were studied: normal controls, those with inflammatory arthritis, and three groups with arthritis treated with bisphosphonate. To determine geometrical properties, image analysis was performed on digitized cross sections of the femoral metaphyseal cortices. The results demonstrated that the posterior cortical wall was significantly less thick in rabbits with arthritis than in normal rabbits and in the rabbits in the three bisphosphonate treatment groups (p < 0.05). Moment of inertia about the lateral-medial axis was reduced in rabbits with arthritis compared with normal rabbits (p < 0.05). Cross-sectional area was not significantly different between groups. The changes suggest a mechanism of weakening of bone in arthritis; when the results are coupled with results of previous porosity studies, severe directional weakness is apparent. Bisphosphonate was effective in preserving bone integrity in inflammatory arthritis.

Animals↗
PubMed1984

Epiphyseal fractures in children treated for osteosarcoma of the femur with chemotherapy, tumourresection, and endoprosthesis: report of four fractures in two children.

This paper reports on two patients, who both were under treatment for osteosarcoma of the femur. Treatment consisted of chemotherapy, resection of the tumour, and reconstruction with an endoprosthesis . Both patients sustained an epiphyseal fracture on two occasions after a minor trauma. Careful observations of the x-rays, including tomography, reveals that a metaphyseal anomaly could be the cause of these fractures. It is suggested that these metaphyseal changes are caused by chemotherapeutic agents. All fractures healed well after a conservative treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1975

Bone growth changes in pyridoxine-deficient rats.

Male and female rats were fed a commercial diet lacking pyridoxine. Using radiological and histological methods the growth of the long bones in the pyridoxine-deficient rats from 2 wk to 6 mth of age was compared with that in paired-fed and in paired-weight-gain control rats of the same age and sex given the same diet supplemented by daily injections of pyridoxine hydrochloride. Measurements of tibial bone length were significantly reduced in the deficient male rats but not females, possibly due to the reduced requirements for growth in the female. Thin epiphyseal plates were a feature of the limb radiographs in all the pyridoxine-deficient rats. Histologically the growing long-bone ends showed a diminished activity of endochondral ossification with thin epiphyseal cartilage and fewer shorter, broad and irregular bone trabeculae in the metaphyses of the deficient rats. These metaphyseal changes resemble those described in starvation.

Animals↗
PubMed1996

Haploinsufficiency of parathyroid hormone-related peptide (PTHrP) results in abnormal postnatal bone development.

Although apparently phenotypically normal at birth, mice heterozygous for inactivation of the gene encoding parathyroid hormone-related peptide (PTHrP) develop haplotype insufficiency by 3 months of age. In addition to histologic and morphologic abnormalities similar to those seen in homozygous mutants, heterozygous animals demonstrated alterations in trabecular bone and bone marrow. These included metaphyseal bone spicules which were diminished in volume, irregularly distributed, and less well developed than those seen in age-matched controls as well as bone marrow, which contained an inordinate number of adipocytes. A substantial reduction in PTHrP mRNA was detected in heterozygous tissue, while circulating parathyroid hormone (PTH) and calcium concentrations were normal. Thus, while a physiologic concentration of PTH was capable of maintaining calcium homeostasis, it was incapable of compensating for PTHrP haploinsufficiency in developing bone. In normal animals, both PTHrP and the PTH/PTHrP receptor were expressed predominantly in chondrocytes situated throughout the proliferative zone of the tibial growth plate. In the metaphysis, the PTH/PTHrP receptor was identified on osteoblasts and preosteoblastic cells situated in the bone marrow, while PTHrP was expressed only by osteoblasts. These observations indicate that postnatal bone development involves susceptible pathways that display exquisite sensitivity to critical levels of PTHrP and imply that the skeletal effects of PTH are influenced by locally produced PTHrP. Moreover, identification of both the ligand and its N-terminal receptor in metaphyseal osteoblasts and their progenitors suggests an autocrine/paracrine role for the protein in osteoblast differentiation and/or function. Impairment in this function as a consequence of PTHrP haploinsufficiency may critically influence the course of bone formation, resulting in altered trabecular architecture and perhaps low bone mass and increased bone fragility.

Age Factors↗
PubMed2000

A New Scale to Assess Culture-Specific Beliefs and Attitudes about Epilepsy.

A new rating scale to assess cultural diversity in North American people's understanding of epilepsy was developed and its psychometric properties were evaluated. The content of the scale was based on the hypotheses that cultural diversity and experience with epilepsy would be associated with differences in people's beliefs and attitudes about epilepsy. The sample, 117 Caucasians, 71 South Asians, and 40 East Asians, was drawn from a larger study. All participants had completed the newscale, Epilepsy Beliefs and Attitudes Scale (EBAS). Cronbach's coefficient alpha for the items in the scale was 0.85. A method of principal-axis factor analysis yielded three factors which were referred to as the Neurological, Enviro-psycho-physical, and Metaphysical subscales to emphasize the underlying themes of beliefs and attitudes they represented. A multivariate analysis of variance (MANOVA) revealed a significant main effect for culture (P < 0.0001), epilepsy status (Caucasians only) (P < 0.007), and epilepsy familiarity group (P < 0.002). Further analysis was conducted between demographic variables, culture, and participants' subscale scores. Results indicated that age, gender, and education were not related to differential responses to the scale. However, a significant effect for the duration of stay in North America was found (P < 0.02). An examination of the role of faith in higher power revealed that the participants may consider both the Neurological and Metaphysical beliefs concurrently. The results provided support for the EBAS as a reliable, valid, and culturally sensitive instrument.

Journal Article↗
PubMed1994

Effects of lead exposure on skeletal development in rats.

The effects of lead on growth in female rats and on growth and skeletal development in their offspring were investigated. No alteration in growth rate, compared to the growth rate in pair-fed controls, was observed in 48 weanling females continuously exposed to 250 or 1000 ppm lead in drinking water and fed a replete diet. After 49 days of exposure, all rats (24 pair-fed controls, 12 exposed to 250 ppm lead, and 12 exposed to 1000 ppm lead) were mated with control males. At parturition, six lactating dams each from the 250 and 1000 ppm lead groups were removed from lead exposure and given control drinking water, and six lactating dams each from the control group were given either 250 or 1000 ppm lead in drinking water. Exposure conditions for the remaining dams in the control, 250, and 1000 ppm groups were not changed. Maternal blood lead in the continuously lead-exposed groups was higher at the end of lactation than prior to mating. Lead exposure prior to parturition caused greater maternal tibial lead accumulation than lead exposure after parturition. In contrast, lead exposure prior to parturition had a lesser impact on offspring tibial lead accumulation than lead exposure after parturition. Decreases in tibial calcium and phosphorus were observed in dams exposed continuously to 250 or 1000 ppm lead; however, there was no apparent effect of lead on maternal growth-plate morphology or on growth-plate width. Offspring body weight was depressed relative to controls during suckling (Day 11) and after weaning (Day 24) in high-dose and continuously lead-exposed groups. Continuous lead exposure caused a greater decrease in offspring body weight than lead exposure only prior to or after parturition. Decreased tail length growth suggested possible effects of lead on tail vertebral bone growth. While tibial calcium and phosphorus levels were not changed in the weanlings, increased weanling growth-plate width, with disruption of chondrocyte organization, and wider metaphyseal trabeculae were observed. Although the mechanisms of these effects are not known, the results suggest that local lead-related effects on growth-plate chondrogenesis and metaphyseal mineralization may be involved.

Animals↗
PubMedDate not supplied

Prediction of peripheral fracture risk by quantitative microdensitometry.

BACKGROUND: The purpose of the study was to investigate whether quantitative microdensitometry (QMD) could be used for screening purposes to identify a population with a high risk for peripheral osteoporotic fractures. METHODS: In 1984 bone mineral density (BMD) measurements were made on the index finger of 612 women. Repeated BMD measurements were obtained in 1989 in 440 women. Cox proportional hazards models were used to obtain adjusted estimates of the hazard ratio of a fracture according to BMD or bone loss. Receiver operating characteristic curves were constructed and the areas under the curves (AUC) were compared. RESULTS: Thirty-five women experienced peripheral osteoporotic fractures between the first and the second measurement. Women in the three lowest quartiles of bone density were 1.4-1.8 times (diaphyseal site) and 2.4-2.8 times (metaphyseal site) as likely to experience a fracture as those in the highest quartile. Women in the quartile with the highest bone loss had a risk of 6.9 (diaphyseal site) and 7.5 (metaphyseal site) times higher than women in the lowest quartile. The discriminative power of the measurement as a single test was moderate (AUC 63%); two successive measurements, made with an interval of 5 years to measure bone loss, increased the discriminating power (AUC 74%; P < 0.05). CONCLUSIONS: Phalangeal BMD and bone loss, as measured by QMD, are important risk factors for peripheral osteoporotic fractures, but cannot be used as an efficient screening instrument for selecting women with the highest fracture risk.

Absorptiometry, Photon↗
PubMed1993

Benign osteopetrosis: a review of 42 cases showing two different patterns.

Radiographs of 42 patients with benign osteopetrosis were reviewed. Clinical notes were available for approximately half of these. According to the classification of Bollerslev and Andersen in 1987, 29 patients had type II disease of whom 18 sustained fractures. Thirteen patients had type I disease; only one of these patients sustained fractures. Transverse banding of the metaphyses was a common feature in type II disease; it was not seen in any of the type I cases. This review confirms that type II patients are at high risk of fracture, while type I patients are not. The presence of sclerotic metaphyseal bands distinguishes between the two types, its presence being enough to confirm type II. However, its absence is not an indication of type I disease, since it is not seen in all cases of type II. Banding does not correlate with liability to fracture. Typing patients with the benign form of osteopetrosis is important in order to anticipate the fracture pattern.

Bone and Bones↗
PubMed1981

Electron-microscopic microprobe analysis on the initial stages of mineral formation in the epiphyseal growth plate.

Dry thin sections (300-500 nm thick) of shock-frozen, freeze-dried and embedded epiphyseal growth plates from the proximal tibia of guinea pigs were cut longitudinally from the plate. Dark round bodies (phi less than 0.5 micron) were observed using the scanning transmission mode of the electron microscope initially directly in the vicinity of the chondrocytes. They gradually spread out in the direction of the metaphysis to the center of the longitudinal septum and represent most probably the matrix vesicles. By use of a microscan of 0.25 X 0.25 micron the element-concentrations of these bodies were measured. The measurements started on those bodies that could be clearly recognized and were extended to a length of 30-40 micron in the metaphyseal direction. To obtain approximate quantitative results the registered CaK alpha and PK alpha x-ray counts were directly compared with counts of fully mineralized regions, the Ca and P contents of which are known. Ca as well as p could be detected in the first visible vesicle-like structures (Ca approximately 0.2%, P approximately 0.4%) and increased steeply in the metaphyseal direction, amounting to approximately 6% Ca and 3% P. These results may lead to the conclusion that Pi becomes split from phosphate esters and transformed into the matrix vesicles already in a very early stage of enrichment. Incorporation of Ca may be coupled with this process.

Animals↗
PubMed1992

The periphysis and its effect on the metaphysis: I. Definition and normal radiographic pattern.

The zone of Ranvier and the ring of LaCroix, together with the membranous bone bark they produce, are termed the periphysis in order to emphasize their normal effect (the metaphyseal collar) on the metaphysis of the infant and young child. In the first 7 years of life, the normal collar at the wrist is 1-3 mm wide. The step-off between the metaphyseal collar and the curvilinear metaphysis, at the margin of the periphysis, should not be mistaken for abuse fracture. The periphyseal bone bark may be radiologically visible at the edge of the physis at the distal ulna in 9% of infants and should not be mistaken for fracture or rickets.

Bone Development↗
PubMed1991

Case report 632. Parosteal osteochondromatous hamartoma associated with Trevor's disease (dysplasia epiphysealis hemimelica).

The current case represents a patient with classic plain film findings of Trevor's disease (DEH) seen in the foot and ankle, who presented with a large, eccentric metaphyseal lesion in the ipsilateral distal femur. The radiographic and pathologic characteristics of this large metaphyseal lesion were considered atypical for a simple osteochondroma; therefore, we propose the term "parosteal osteochondromatous hamartoma" as a descriptive term that best fits its unique characteristics.

Child↗
PubMed1992

Extracellular alkaline phosphatase activity in mineralizing matrices of cartilage and bone: ultrastructural localization using a cerium-based method.

The ultrastructural localization of alkaline phosphatase (A1P) activity has been demonstrated in epiphyseal growth cartilage and metaphyseal bone of rats. Epiphyso-metaphyseal specimens were decalcified with EDTA and treated with MgCl2 to regenerate the enzymatic activity before incubation in a medium containing beta-glycerophosphate, MgCl2 and CeCl3. A1P activity was present on the outer surface of the plasmamembrane of maturing and hypertrophic chondrocytes and of osteoblasts. Moreover, the reaction product was present in chondrocyte lacunae, in matrix vesicles, and in cartilage matrix, as well as among uncalcified collagen fibrils of osteoid tissue in bone. The intensity of reaction was the lowest, or completely lacking, where the degree of matrix calcification was the highest. These results suggest that alkaline phosphatase is transported from the cells into the cartilage and bone matrix by its association with matrix vesicles and plasmamembrane components, and that its activity in cartilage and bone matrix is inhibited as it is incorporated in the mineral substance.

Alkaline Phosphatase↗
PubMed1992

Production of new trabecular bone in osteopenic ovariectomized rats by prostaglandin E2.

Serum chemistry and bone morphometry of the proximal tibial metaphysis were performed in 3-month-old double fluorescent-labeled, female Sprague-Dawley rats subjected to bilateral ovariectomy or sham surgery for 4 months prior to treatment with 0, 0.3, 1, 3, or 6 mg of prostaglandin E2 (PGE2)/kg/day subcutaneously for 30 days. The 4-month postovariectomized rats possessed an osteopenic proximal tibial metaphysis with 7% trabecular area compared with controls (19%). PGE2 treatment elevated osteocalcin levels and augmented proximal tibial metaphyseal bone area in ovariectomized and sham-operated rats. Osteopenic, ovariectomized rats treated with 6 mg PGE2/kg/day for 30 days restored bone area to levels of age-matched sham-operated rats. Morphometric analyses showed increased woven and lamellar bone area, fluorescent-labeled perimeter (osteoblastic recruitment), mineral apposition rate (osteoblastic activity), bone formation rate (BFR/BV), and longitudinal bone growth. These dramatic bone changes were all significantly increased at the dose-response manner. This study showed that in vivo PGE2 is a powerful activator of bone remodeling, it increases both bone resorption and bone formation, and produces an anabolic effect by shifting bone balance to the positive direction. Furthermore, PGE2-induced augmentation of metaphyseal bone area in ovariectomized rats was at least two times greater than in sham-operated rats.

Alkaline Phosphatase↗
PubMed1993

Growth hormone involvement in the regulation of tartrate-resistant acid phosphatase-positive cells that are active in cartilage and bone resorption.

Young male Sprague-Dawley rats (5-7 weeks old, 80-120 g) were hypophysectomized (HX) and maintained on thyroxin and dexamethasone replacement therapies. Ten days after surgery, some HX rats received a single injection of human growth hormone (hGH), and others five daily injections of hGH. Tartrate-resistant acid phosphatase (TRAP) histochemistry was employed in order to evaluate the number of cells of resorptive potential in the metaphyseal bone of the proximal tibiae of HX rats and was compared with normal rats and HX rats that further received hGH replacement therapy. In normal rats, two populations of TRAP-positive cells were identified: multinuclear cells, which showed histological characteristics of osteoclasts, and small mononuclear cells, the number of which was overwhelming when compared with the number of TRAP-positive multinuclear cells. Both populations were reduced in the HX rat, but more so the mononuclear cells, which were assumed to represent the precursor pool of mature osteoclasts and chondroclasts (P < 0.005). Five daily injections of hGH to HX rats brought about a significant increase in the number of TRAP-positive multinuclear cells, the number of nuclei of these cells, and the number of mononuclear TRAP-positive cells, throughout the metaphyseal bone (P < 0.05). A single injection of hGH increased only the number of TRAP-positive multinuclear cells in the trabecula/bone marrow interface (P < 0.05), indicating a very rapid fusion of precursor cells into mature osteoclasts in that particular location.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗
PubMed1994

Differential effects of insulin and insulin-like growth factor-I in the femoral tissues of rats with skeletal unloading.

The alteration of bone metabolism in the femur of rats with skeletal unloading for 4 days was investigated. Skeletal unloading was designed using the model of hindlimb hang in rats. Skeletal unloading caused a significant decrease in femoral weight, calcium, and phosphorus contents in the metaphysis but not diaphysis. Also, the unloading induced a significant decrease of zinc content, alkaline phosphatase activity, and deoxyribonucleic acid (DNA) content in the femoral diaphysis and metaphysis. When the femoral-diaphyseal and metaphyseal tissues from normal and skeletal-unloading rats were cultured in the presence of insulin (10(-9) and 10(-8) M) for 24 hours in vitro, the hormonal effect to increase alkaline phosphatase activity and DNA content in the diaphysis, but not metaphysis, was lost in the bone tissues from unloading rats. However, the culture with insulin-like growth factor-I (IGF-I; 10(-8) and 10(-7) M) produced a significant increase of alkaline phosphatase activity and DNA content in both the diaphyseal and metaphyseal tissues from normal and unloading rats. These results demonstrate that skeletal unloading causes an impairment of insulin effect, but not IGF-I effect, on bone metabolism in femoral tissues.

Alkaline Phosphatase↗