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PubMed1999

Chronic alcohol consumption during male rat adolescence impairs skeletal development through effects on osteoblast gene expression, bone mineral density, and bone strength.

BACKGROUND: The effect of chronic alcohol ingestion on bone formation is mediated through its direct actions on osteoblasts. The affected population of mature osteoblasts declines in both number and function resulting in decreased cancellous bone volume and cortical bone strength. Although the mechanism of action on osteoblasts is unknown, alcohol alters osteoblast gene expression and matrix synthesis. METHODS: Male rats consuming alcohol (EtOH) daily for 60 days from 35 days of age until 95 days of age (unrecovered group) were compared to rats switched to a regular diet of rat chow without EtOH for an additional 90 days (recovered group). The effects of chronic dietary EtOH on skeletal development during adolescence were examined in the unrecovered and recovered rats by hormonal analysis, bone mineral density determination, bone histomorphometry, metaphyseal gene expression for osteoblast-specific proteins, and biomechanical analysis. RESULTS: The unrecovered EtOH imbibing rats weighed less than their paired isocaloric-fed and ad libitum mates. Statistically significant reductions occurred in femur lengths in the unrecovered EtOH-fed group compared to controls. Serum testosterone levels were significantly decreased by EtOH consumption but returned to higher normal levels during the recovery period. Serum insulin-like growth factor-1 (IGF-1) levels were unaffected by EtOH. Serum osteocalcin levels in the unrecovered EtOH-fed group were higher than those in the recovered group but EtOH intake did not elevate the unrecovered levels compared to isocaloric or ad libitum control rats. Quantitative computed tomography (QCT) determination of bone mineral density (BMD) revealed a statistically significant reduction only in the distal femur metaphysis in the unrecovered EtOH-fed rats. BMD increased during recovery in the distal femur metaphysis and femur mid-cortex. Image analysis of midsagittal sections of the proximal tibial metaphysis of unrecovered rats revealed reductions in cancellous area, trabecular cellularity and thickness, and increased trabecular separation. Cortical widths were significantly reduced by chronic EtOH consumption. These changes remained statistically significant at the end of the recovery period. Four-point biomechanical testing of femurs from EtOH-fed and control unrecovered groups revealed significant reductions in cortical strength, energy-to-failure, and stiffness. These cortical characteristics returned to normal values with abstinence. Tibial metaphyseal alpha-1 type I collagen and osteocalcin mRNA expression levels were significantly elevated above the paired isocaloric control levels after 60 days of EtOH consumption. Metaphyseal alkaline phosphatase mRNA levels remained unaltered by EtOH consumption in the unrecovered group. After 90 days of abstinence alpha-1 type I collagen and alkaline phosphatase gene expression levels remained significantly elevated over the isocaloric and ad libitum control levels (collagen) and the isocaloric control value (alkaline phosphatase). However, metaphyseal osteocalcin mRNA levels declined to normal levels during abstinence. CONCLUSIONS: Chronic consumption of EtOH during the peripubertal period of skeletal growth leads directly to decreased metaphyseal and cortical bone mediated through effects on osteoblasts. Removal of EtOH from the diet is accompanied by incomplete restoration of normal bone metabolism during skeletal growth.

Age Factors↗
PubMed2002

Coexistence of primary bone tumours: report of 4 cases of collision tumours.

OBJECTIVE: To report, in 4 patients, the occurrence of 2 different primary tumours in proximity in the same bone. Three patients had osteosarcomas, and 1 had a giant cell tumour; all had coincident metaphyseal fibrous defect. METHODS: Four patients (2 women, 1 man and 1 boy; 18, 25, 24 and 10 years of age, respectively) presented with progressive pain in the knee and distal thigh. All were studied by radiography, magnetic resonance imaging was done in 3 patients, and diagnostic open biopsy was performed for all. RESULTS: Radiologic studies demonstrated tumours in the distal end of the femur in all 4 patients. Biopsy tissue showed a metaphyseal fibrous defect in all, with coexistence of an associated giant cell tumour in 1 patient and an osteosarcoma in each of the others. In all cases, the metaphyseal fibrous defect was penetrated by the adjacent tumour. CONCLUSIONS: Despite the relative prevalence of metaphyseal fibrous defect, giant cell tumour and osteosarcomas in the distal end of the femur and their occurrence in approximately the same age group, their association has rarely been reported. As both giant cell tumours and osteosarcomas are usually diagnosed late in their clinical course, they may outgrow and destroy any evidence of pre-existing metaphyseal fibrous defect. The rate of destruction is also influenced by the distance between the 2 lesions--the shorter the distance, the earlier the destruction.

Adolescent↗
PubMed1988

The rate of bony tissue deposition in the spongiosa of the extremities of long bones in the dog.

9 mongrel dogs ranging from 5 months to 3 years of age were given 3 single endovenous Alizarin injections at 20-day intervals. In transverse sections of the epiphyses and metaphyses of the proximal and distal ends of the femur, tibia, radius and humerus, we measured the thickness of the bony tissue newly formed during the period between the 1st and 2nd Alizarin administration, and separately of that laid down between the 2nd and the 3rd. The weighted means and histograms set up by us of the values severely gathered in the tubular (peripheral) and lamellar (deeply placed) spongiosa in each metaphyseal and epiphyseal sections, are the expression of the mean linear rate of bony tissue deposition. The mean linear rate of bone deposition (1) declines with age; (2) is higher in the metaphyses than in the epiphyses; (3) in single metaphyses it is higher in the tubular than in the lamellar type of trabeculae. These differences are much marked in the animals undergoing body growth, tending to become appreciably reduced in adult specimens. Significant differences in bone deposition rates between corresponding regions of different bones from the same individual were not seen to occur. The differences in bony tissue deposition rate between the tubular and lamellar spongiosa networks seem to depend upon the action exerted by local factors functionally closely associated with the remodelling of metaphyses during growth in length of the skeletal segments, hence upon predominantly mechanical factors.

Animals↗
PubMed1983

Effect of dietary calcium on the response of bone to 1,25 (OH)2D3.

The purpose of this investigation was to evaluate, by static and dynamic histomorphometry, the comparative influence of dietary calcium on the effect of 1,25(OH)2D3 on bone. Young adult female rats were fed a diet containing 0.3% phosphorus and 0.05%, 0.5%, or 1.0% calcium. Rats in each group received placebo, or 27 ng or 135 ng of 1,25(OH)2D3, intraperitoneally, for 10 days. A dramatic osteosclerosis and hyperosteoidosis characterized by an increase in metaphyseal hard tissue percentage and percentage metaphyseal osteoid, a decrease in osteoclasts per millimeter of trabecular surface perimeter and longitudinal growth, and hypertrophy of osteoblasts developed in the proximal tibial metaphysis of rats fed 1.0% calcium diet and given 135 ng of 1,25(OH)2D3 compared with placebo-treated rats fed the same diets. Similar histomorphometric changes, with the exception of increased metaphyseal hard tissue percentage, occurred in rats fed 0.5% dietary calcium and treated with 135 ng of 1,25(OH)2D3. Metaphyseal hard tissue percentage, percentage metaphyseal osteoid, and osteoclasts per millimeter of trabecular surface perimeter were not affected by treatment with 135 ng of 1,25(OH)2D3 in rats fed a 0.05% calcium diet. Serum calcium was significantly elevated in all 1,25(OH)2D3-treated rats. Dietary calcium appears to modulate the effects of 1,25(OH)2D3 on bone. Only diets containing adequate dietary calcium permit exogenous pharmacologic levels of 1,25(OH)2D3 to produce a positive skeletal balance either by decreasing osteoclasis and/or increasing bone matrix synthesis.

Animals↗
PubMed1995

Bone growth and modeling changes induced by periosteal stripping in the rat.

In this study, the changes in longitudinal bone growth and metaphyseal modeling induced by middiaphyseal periosteal stripping in the rat femur were analyzed by means of histomorphometrical techniques. One hundred forty-four male 30-day-old Sprague-Dawley albino rats distributed in 4 groups of 36 were studied: a control group, a sham group, a group with middiaphyseal right femoral periosteal stripping, and a group with a polyethylene ring wrapped around the stripped zone. The animals were euthanized at 1, 2, or 4 weeks from the start of the experiment, after double tetracycline labeling. A statistically significant, albeit small, longitudinal overgrowth of stripped femurs was observed after a latency period of 2 to 4 weeks. The metaphyseal diameters were greater in stripped femurs than nonstripped femurs. This finding was associated with a lower osteoclastic index in the external metaphyseal surface and with a lower bone formation rate in the internal surface of the metaphyseal cortex. These latter findings have not been reported previously in the literature and may support the role of the periosteum in controlling metaphyseal modeling.

Animals↗
PubMed1997

Tibial insert undersurface as a contributing source of polyethylene wear debris.

Sixty-seven ultrahigh molecular weight polyethylene tibial inserts from cementless total knee arthroplasties were retrieved at autopsy and revision surgery and analyzed for evidence of articular and nonarticular surface wear after a mean implantation time of 62.8 months (range, 4-131 months). Polyethylene cold flow and abrasive wear on the nonarticular insert surface (undersurface) were assigned a wear severity score (Grade 0-4). The severity of articular wear was assessed quantitatively and graded. Corresponding prerevision radiographs were evaluated for evidence of tibial metaphyseal osteolysis and osteolysis around tibial fixation screws. Exact nonparametric conditional inference methods were used to establish correlations between different variables and the occurrence of tibial metaphyseal osteolysis. Severe Grade 4 wear of the tibial insert undersurface was associated with tibial metaphyseal osteolysis or osteolysis around fixation screws. Time in situ statistically was related to Grade 4 undersurface wear and tibial metaphyseal osteolysis. The occurrence of tibial osteolysis was not related statistically to articular wear severity, insert thickness, or implant type. The main articulation between the femoral implant and ultrahigh molecular weight polyethylene insert has been assumed to be the primary source of polyethylene debris contributing to osteolysis and total knee arthroplasty implant failure. The undersurface of the insert is an additional source of polyethylene debris contributing to tibial metaphyseal osteolysis. To lessen polyethylene debris produced at this modular interface, the tibial implant locking mechanism should fix the insert firmly to the metal backing to decrease relative micromotion. Because motion between the insert and metal backing may be inevitable, the wear characteristics of the inner tray surface should be optimized to minimize wear debris production at this other articulation.

Arthroplasty, Replacement, Knee↗
PubMed1999

Was Kent a Hahnemannian?

This article voices concern at the trend among an influential section of homeopaths the world over, to jettison Hahnemann's similimum principle and replace it with Kent's almost exclusive concentration on mental and psychic symptoms. This concern raises the question whether Kent was a true Hahnemannian. In order to discuss this question, two schools of thoughts are investigated. The first argues that Hahnemann's theories were scientific whereas Kent's were metaphysical. The second criticises Kent's more severely for being metaphysical. At the same time, it accuses Hahnemann himself of increasingly losing his way, with increasing age, into metaphysical homeopathy. The author believes there was no break in Hahnemann's thinking as alleged, but a gradual development with increasing experience, together with judicious use of rational insight, when scientific explanation was not yet available. The yardstick used to accuse Hahnemann of being metaphysical is crudely empirical and long outdated.

History, 19th Century↗
PubMed1994

Perspectives: a vital biomechanical model of the endochondral ossification mechanism.

BACKGROUND: Mechanical usage effects could explain many features of endochondral ossification and related processes. Mineralization of growth plate cartilage could reduce its mechanical strains enough to make its resorption begin and to guide it in space. By removing most of its mineralized vertical septae, resorption could overload the remainder enough to increase woven bone formation on them and construct the primary spongiosa. After it finishes mineralizing, the primary spongiosa could become stiff enough to begin partial disuse in strain terms, so BMU-based remodeling would begin replacing it with lamellar bone. This would construct the secondary spongiosa. In transferring loads from the growth plate to the cortex, the central metaphyseal spongiosa becomes deloaded. This disuse would make remodeling remove it in the diaphyseal marrow space. METHODS: The slow growth of epiphyses and apophyses gives their spongiosas more time to adapt to their loads than the metaphyseal spongiosa beneath faster growing growth plates. Compared to metaphyseal trabeculae, this leads to fewer and thicker epiphyseal trabeculae that turn over more slowly and should persist for life because they carry loads for life. RESULTS: Rapid turnover of metaphyseal cortex in very young subjects could let it strain enough to form woven bone. Increased thickness and slower turnover of this cortex in older subjects could reduce its strains enough to make lamellar bone form there instead. This would compose this cortex mostly of woven bone in the very young and of lamellar bone in adults. CONCLUSIONS: This model assigns particular importance to the stiffness and strains of tissues (as distinguished from their strength and stresses), to the relative rates of some processes, and to responses of the skeleton's biologic mechanisms to a tissue's typical largest mechanical strains (as distinguished from their stresses).

Adult↗
PubMed1991

Electromagnetic stimulation of bone repair: a histomorphometric study.

The effect of pulsing electromagnetic fields (PEMFs) on bone repair was studied in principal metacarpal bones of eight adult male horses: Six horses were treated with PEMFs, and two horses were untreated. In treated horses, Helmholtz coils were applied during a 60-day period to the left metacarpal bones, bored with eight holes of equal diameter and depth, from the middiaphysis toward the distal metaphysis. Eight equal holes bored in the right metacarpal, surrounded by unactivated Helmholtz coils, were taken as controls. The two untreated horses were taken as additional control. The results of computer-assisted histomorphometric analysis indicate that (a) in diaphyseal levels, the amount of bone formed during 60 days is significantly greater (p less than 0.01) in PEMF-treated holes than in contralateral ones and those in control horses; (b) in metaphyseal levels, PEMF-treated holes are sometimes more closed, sometimes less, as compared with contralateral holes and those in control horses; in any case the statistical analysis indicates that the symmetry in the rate of hole repair, found between the two antimeres of control horses, is not appreciable at metaphyseal levels also; (c) there was no statistically significant difference between untreated holes in PEMF-treated horses and holes in control horses, neither at diaphyseal nor at metaphyseal levels. These preliminary findings indicate that PEMFs at low frequency influence the process of bone repair on both diaphysis and metaphysis, and seem to improve the process of bone repair in skeletal regions normally having a lower osteogenetic activity, i.e., in diaphyses as against metaphyses.

Animals↗
PubMed1980

Bone cell kinetics during longitudinal bone growth in the rat.

The purpose of this work was to provide futher knowledge about bone cell kinetics in the metaphysis of the growing long bone. Seventy rats were sacrificed from 1 to 120 h after injection of tritiated thymidine. Autoradiographs of 3 micrometers thick sections of the proximal tibial metaphysis were studied in a manner which allowed evaluation of labeled cell nuclei as a function of increasing age of metaphyseal tissue. A cell cycle duration study for osteoprogenitor cells was done. Labeled osteoprogenitor cells and osteoblasts first appeared at 1 h post-injection. The great majority of all labeled osteoprogenitor cells and osteoblasts was found within 1 mm of the growth cartilage-metaphyseal junction (GCMJ) at all times, apparently migrating with the moving GCMJ. In contrast, labeled osteoclast nuclei first appeared at 24 h post-injection within 0.3 mm of the GCMJ and remained always with the area of bone surface with which they were first associated, even as the GCMJ migrated away. By 5 days post-injection, the source of new labeled osteoclast nuclei in the metaphysis near the GCMJ was depleted, whereas that for the osteoblasts remained. The existence of two kinetically different, as well as ultrastructurally different, members of the metaphyseal osteoprogenitor cells population is postulated. A cell cycle time of 39 +/- 18 h was found for the osteoprogenitor cell population, but has limited meaning. A schema for metaphyseal bone cell movements during longitudinal bone growth is presented.

Aging↗
PubMed1986

Quantitative morphometric evaluation of the inhibitory activity of new aminobisphosphonates on bone resorption in the rat.

Three new bisphosphonates of various chain length, namely, 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (AHBuBP), 5-amino-1-hydroxypentylidene-1,1-bisphosphonate (AHPeBP), and 6-amino-1-hydroxyhexylidene-1,1-bisphosphonate (AHHexBP) were compared with 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP), and dichloromethylene bisphosphonate as to their effect on metaphyseal bone remodeling in the rat. The parameters assessed were growth in length, mineralization, metaphyseal density, mean trabecular diameter, and number of trabeculae. Both metaphyseal density, an index of metaphyseal Ca balance, and number of trabeculae, an index of bone resorption, showed the following sequence of potency: AHBuBP greater than AHPrBP = AHPeBP = AHHexBP greater than Cl2MBP. All compounds decreased trabecular diameter somewhat, an index of bone formation, with AHBuBP decreasing the least. AHBuBP and possibly AHHexBP appear to be interesting new bisphosphonates for future clinical use.

Animals↗
PubMed2001

Role of endogenous zinc in the enhancement of bone protein synthesis associated with bone growth of newborn rats.

The role of endogenous zinc in protein synthesis in the bone tissues of newborn rats was investigated in the present study. Femoral-diaphyseal and metaphyseal tissues were obtained at 1, 7, 14, 21, and 28 days after birth. Many protein molecules were found to be present in the diaphyseal and metaphyseal tissues using sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. Bone protein synthesis activity was enhanced by increasing age, and reached a plateau 21 days after birth. Protein synthesis in the diaphyseal and metaphyseal tissues obtained from 7- or 14-day-old rats was significantly decreased by the addition of dipicolinate (10(-3) M), a chelator of zinc ion, into the reaction mixture. while it was significantly enhanced by zinc sulfate (10(-4) M). When the diaphyseal and metaphyseal tissues obtained from 7- or 14-day-old rats were cultured for 48h in a medium containing dipicolinate (10(-3) M), bone protein synthesis was significantly reduced. This decrease was blocked completely by culture with the addition of zinc (10(-4) M). Culture with zinc (10(-5) and 10(-4) M) alone had a stimulatory effect on the bone protein synthesis. Zinc (10(-4) M)-induced increases in bone protein synthesis were completely blocked by culture with cycloheximide (10(-6) M) or actinomycin D (10(-7) M). The present study suggests that bone protein synthesis is enhanced with increasing age of newborn rats, and that endogenous zinc in bone tissues has a stimulatory role in the enhancement of protein synthesis with bone growth.

Aging↗
PubMed1991

Determinants of bone mineral content in childhood.

In a sample of 1190 children (574 boys and 616 girls), aged 6.8-10.7 years, bone mineral content was studied using quantitative röntgen microdensitometry (QMD) at the diaphyseal and the metaphyseal site of the left second digit. Percentile curves of bone mineral density was determined by skeletal age for boys and girls separately. Bone mineral content at the diaphyseal site was significantly associated with skeletal age, height and body weight in boys and girls and with chronological age at the metaphyseal site in boys. In girls higher levels of bone mineral content were observed in those with a skeletal age greater than 7.3 years, compared to those with a skeletal age equal to or less than 7.3 years, adjusted for height and body weight. In boys a higher level of bone mineral content was found in those with a height greater than 138 cm, adjusted for skeletal age, compared to those with a height equal or less than 130 cm, at the diaphyseal and metaphyseal site. Girls with a relatively higher body weight had lower levels of bone mineral content at the metaphyseal site.

Age Determination by Skeleton↗
PubMed1986

Reversibility of nontraumatic disuse osteoporosis during its active phase.

The potential for the recovery of bone lost during the active phase of disuse osteoporosis, both in the diaphyseal compacta and metaphyseal spongiosa was tested in young adult and old Beagle dogs. Immobilization for up to 60 weeks was achieved by placing the forelimb in a spica cast and remobilization by removing it. Bone volume was estimated in the third metacarpus, radius, ulna and humerus at the mid-diaphysis and at the level of distal metaphyseal spongiosa in both forelimbs by radiography and histomorphometry. Measurements carried out on animals remobilized showed considerable recovery of the original bone loss. In both age groups, the residual deficits increased, however, with the duration of immobilization and were similar in the metaphyseal spongiosa and in the diaphyseal compacta. The old dogs which began the study with 10% less bone than the younger dogs, showed smaller proportional losses than the younger dogs but greater residual deficits, most evident in the diaphysis. In both age groups the distal, weight-bearing bones tended to show greater losses and also greater recovery both in diaphyseal compacta and the metaphyseal spongiosa. Thus, 28 weeks after cast removal following 32 weeks of immobilization the following findings were noted: In the third metacarpal diaphyseal compacta in the younger dogs, a 53.6% loss (mostly from the periosteal envelope) decreased to 16.3% (a 70% recovery) while in the older dogs a 37.6% loss (mostly from the endosteal envelope) decreased to 23% (a 40% recovery).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Genetic variations that regulate bone morphology in the male mouse skeleton do not define its susceptibility to mechanical unloading.

Genetics can substantially influence bone morphology and may define the skeleton's response to mechanical unloading. Recent data indicated that disuse produces different site-specific responses in the skeleton of genetically distinct adult female C3H/HeJ (C3H) and BALB/cByJ (BALB) mice; while disuse BALB mice had significantly less bone than age-matched controls in the distal and diaphyseal femur, the removal of weight bearing had a much smaller influence in C3H. Using adult male mice from these two inbred strains, the hypothesis was tested that interactions between genetic variations and anatomic location define bone morphology and its susceptibility to unloading. Four-month-old male BALB and C3H mice were either subjected to 21 days of hindlimb unloading or served as controls. Multiple cortical and trabecular regions within the distal and diaphyseal femur were analyzed by micro-computed tomography. C3H controls had significantly greater diaphyseal and metaphyseal cortical bone area (45% and 32%) and greater metaphyseal trabecular bone volume fraction (67%) than BALB controls, but epiphyseal trabecular bone volume fraction was similar between the two strains. Despite these substantial, site-specific differences in bone morphology, disuse induced similar changes in bone morphology in these two strains. Compared to controls, disuse BALB and C3H had significantly less metaphyseal (17% and 19%) and epiphyseal (10% and 13%) trabecular bone, while diaphyseal and metaphyseal cortical bone geometry was unaffected. These data indicate that the genetic variations that caused spatially nonuniform differences in trabecular and cortical bone morphology between the two strains had little influence on the susceptibility of a specific site to unloading. Cross-gender comparisons with previous data from female BALB and C3H mice further suggest strong interactions by which gender, genotype, and anatomical location define the response of the skeleton to the removal of weight bearing.

Animals↗
PubMed2007

Long-bone changes after pamidronate discontinuation in children and adolescents with osteogenesis imperfecta.

Cyclical intravenous pamidronate is a widely used symptomatic therapy in moderate to severe osteogenesis imperfecta (OI). The effects of treatment discontinuation on long bone development have not been characterized. In this observational study we used peripheral quantitative computed tomography to assess the radius at the distal metaphysis and at the diaphysis in 23 young OI patients (11 female) who had received pamidronate for at least 3 years. Measurements were performed twice, at the time of treatment discontinuation (when the age of the patients ranged from 5.9 to 21.3 years) and at an average of 1.9 years (range 1.5 to 2.4 years) later. At the time of pamidronate discontinuation, all but one of the patients who were below 15 years of age (n=14) had a positive age- and sex-specific z-score for bone mineral content (BMC) at the metaphysis, resulting in a mean z-score of +2.0 (SD=1.0) for this subgroup. In contrast, patients aged 15 years or older (n=9) had an average metaphyseal BMC z-score of -1.5 (SD=1.5). After pamidronate discontinuation, metaphyseal BMC z-score decreased by an average of 2.4 (SD=2.0) in the whole group. The change in BMC z-score was growth-dependent, as BMC z-scores decreased by about 2 or more in all patients in whom distal radius growth plates were open when pamidronate was discontinued. In contrast, none of the 11 patients with closed distal radius growth plates experienced a decrease in metaphyseal BMC z-score by more than 2. At the diaphysis, the average BMC z-score was low at the time of the last pamidronate infusion [z-score -1.7 (SD=1.4)]. After pamidronate discontinuation, the average diaphyseal BMC z-score decreased by only 0.3 (SD=0.4). In summary, this study shows that the effect of pamidronate discontinuation is much larger at the radial metaphysis than at the diaphysis and is dependent on growth. Metaphyseal bone tissue added by longitudinal growth after treatment discontinuation has a lower density than tissue created during treatment. It is possible that this produces zones of localized bone fragility after pamidronate treatment is stopped in growing children.

Adolescent↗
PubMed2000

Treatment with risedronate or alendronate prevents hind-limb immobilization-induced loss of bone density and strength in adult female rats.

Immobilization leads to rapid loss of bone mass and mechanical competence, and long-term immobilization or repeated periods of short-term immobilization can have serious skeletal consequences and may lead to increased fracture liability. The aim of the present preclinical study was, therefore, to assess whether two antiresorptive agents, risedronate (Ris) or alendronate (Aln), would be capable of preventing immobilization-induced loss of bone mass and strength in rats. The study was designed as a dose-response study, and the site-specific effects of immobilization and of treatment are described. Four-month-old virgin female Sprague-Dawley rats were divided into eight groups with 12 animals in each group: (1) immobilized (Imm) control; (2) normal control; (3) Imm + Ris 0.1 mg/kg body weight/day (b.w./day); (4) Imm + Ris 0.2 mg/kg b.w./day; (5) Imm + Ris 1.0 mg/kg b.w./day; (6) Imm + Aln 0.2 mg/kg b.w./day; (7) Imm + Aln 1.0 mg/kg b.w./day; and (8) Imm + Aln 2.0 mg/kg b.w. /day. In groups 1 and 3-8, the right hind leg was immobilized with an elastic bandage. The study period was 28 days. The effects of unilateral hind-limb immobilization and of treatment were determined by dual-energy X-ray absorptiometry (DEXA) measurements on tibiae and by biomechanical testing of femora at three different sites: diaphysis; femoral neck; and distal metaphysis. Bilateral measurements were performed (on the immobilized and nonimmobilized legs). Immobilization induced a significant loss of bone mineral density (BMD) at the proximal tibial metaphysis, but no change at the mid-diaphysis. Furthermore, immobilization induced a loss of bone strength at the two femoral metaphyses, but no change was seen in three-point bending of the diaphysis. Both risedronate and alendronate treatment showed a dose-dependent protection against the immobilization-induced loss of bone density and strength at the metaphyses. We conclude that, in rats, short-term hind-limb immobilization affects only the metaphyses and that no changes are seen in the diaphysis. Both risedronate and alendronate can prevent immobilization-induced bone loss at the metaphyses. The present study confirms the importance of examining several skeletal sites when testing the efficacy of therapeutic agents.

Alendronate↗
PubMed2002

Simple bone cyst is not a single entity: point of view based on a literature review.

Three varieties of simple bone cysts have not attracted a lot of clinical attention: simple bone cysts in non-tubular bones, multiple cysts and epiphyseal cysts. Simple bone cysts occurring in non-tubular bones form about 4-10% of total cases, with a higher age incidence and better prognosis. Epiphyseal simple bone cysts have a higher age incidence, a lower male/female ratio, a very high humerus/femur ratio and higher incidence of tibial location than the classic metaphyseal cysts. Multiple cysts occur in the higher age group and show very high male predominance. In the review of the literature, 15 cysts (35.7%) were in non-tubular bones and six cysts (14.3%) were epiphyseal. They have a better prognosis than the classic metaphyseal ones. Four clinico-anatomic varieties of simple bone cysts could be recognized: classic metaphyseal, non-tubular, epiphyseal, and multiple. Venous obstruction might be the cause of all forms of the disease but the etiologies of venous obstruction causing the last three clinical forms might be different from that causing the classic metaphyseal ones.

Bone Cysts↗