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Lengthening osteotomy in the metaphysis and diaphysis. An experimental study in the ovine tibia.

In 20 sheep, aged seven to eight months, a tibial lengthening osteotomy was performed to compare the process of repair of the metaphyseal and diaphyseal regions of the bone. Analogous to clinical lengthening, two frame configurations of a bilateral external fixation device were used to obtain adequate fixation of the bone segments in the metaphyseal and diaphyseal lengthening osteotomies. A daily distraction rate of 1 mm for 4.5 weeks yielded an average length increase of 2.6 cm (12.5%). After death at 4.5 weeks postdistraction, the elongated bones were tested mechanically with the contralateral tibiae as controls. No significant difference in relative torsional strength of the elongated tibiae was found between the two groups. Inferior mechanical stability of the bone segments in metaphyseal compared with diaphyseal lengthening (due to differences in frame rigidity and distribution of muscular moments) influenced healing to such an extent that any superior biologic, osteogenic potential in the metaphyseal bone region was nullified. With the clinical use of two configurations of a given external device necessary for fixation of the bone segments in a metaphyseal or diaphyseal lengthening osteotomy, the empirically accepted idea that metaphyseal healing is superior may not be correct.

Animals↗

The arterial anatomy of the developing human dorsal and lumbar vertebral body. A microarteriographic study.

The arterial anatomy of 60 lumbar and lower dorsal vertebral bodies from eight subjects aged between 29 weeks gestation and 15 years was studied. The arteries had been injected with a suspension of barium sulphate and the vertebrae decalcified, sectioned and radiographed. In the specimen of 29 weeks gestation, the equatorial arteries were present. Precursors of the metaphyseal arteries lay obliquely over and completely outside the ossification centre. These precursors originated from an irregular network of perichondral arteries near the equator. By six months of age, the perichondral arteries had migrated discally and had become well organized metaphyseal anastomoses while the metaphyseal arteries had become horizontal. Also by six months, the extra-osseous longitudinal anastomoses had developed into the adult pattern. In the 36 weeks fetus, the ends of the unbranching metaphyseal arteries were incorporated into the ossification centre. This central relationship was maintained into adult life, but, as the ossification centre expanded, the branches of the intra-osseous arteries followed the zone of ossification in a centrifugal manner. In infancy, the metaphyseal arteries were approximately equal in length and the equatorial arteries divided in the middle of the vertebral body; by the age of 15 years, the metaphyseal arteries arising from the anterolateral surfaces were longer than those which arose from the posterior surface, and the equatorial arteries divided behind the mid-point. From these arterial observations, a number of deductions concerning the mode of growth of the vertebral body have been drawn. Preterminal coils and typical peripheral arteries, frequent features in the adult vertebral body, were not seen in any of these specimens. There was no evidence of any epiphyseal growth plate, nor of epiphyseal arteries in these specimens.

Adolescent↗

Rethinking the birthing body: Cartesian dualism and perinatal nursing.

AIM OF THE PAPER: This paper highlights the pervasive influence of a Cartesian metaphysics on the medical paradigm and its profound impact on the practice of perinatal nursing in North America. BACKGROUND: Modern perinatal health care practices are founded on a Cartesian metaphysics that reduce birthing women to the status of object. Such practices deny the holistic aims of perinatal nursing. METHODS: A philosophical inquiry informs the tenets of this metaphysical discussion regarding the foundations of perinatal nursing practices. FINDINGS: Although perinatal health care is founded on a Cartesian metaphysics, an alternative paradigm of embodied practice is suggested as a way of viewing birthing women as embodied subjects. CONCLUSION: If the foundations of health care, which have been built on a Cartesian metaphysics, are not re-examined, perinatal nurses will be providing care that further reduce women to the status of object.

Attitude of Health Personnel↗

Stimulatory effect of zinc on deoxyribonucleic acid synthesis in bone growth of newborn rats: enhancement with zinc and insulin-like growth factor-I.

The effect of zinc on in vitro deoxyribonucleic acid (DNA) synthesis activity in the femoral-diaphyseal and metaphyseal tissues of newborn rats was investigated to determine a role of zinc in bone growth. In vitro DNA synthesis was assayed in a reaction mixture containing the 100 g centrifugation supernatant, which includes the nucleus of bone cells, of bone issue homogenate with incorporation of [3H]-deoxythymidine 5'-triphosphate (dTTP). DNA synthesis activity in the femoral-diaphyseal and metaphyseal tissues of newborn rats was significantly raised with increasing age (1-21 days) after birth. The presence of dipicolinate (10(-3) M), a chelator of zinc, in the reaction mixture caused a significant decrease in DNA synthesis activity in the diaphyseal and metaphyseal tissues of newborn rats at 7 and 14 days after birth. The addition of zinc sulfate (10(-6) - 10(-4) M) resulted in a significant increase in DNA synthesis activity in the diaphyseal and metaphyseal tissues. When the diaphyseal and metaphyseal tissues of newborn rats at 7 days after birth were cultured for 24 hours in a serum-free medium containing either vehicle, zinc sulfate (10(-4) M), insulin-like growth factor-I (IGF-I; 10(-8) M) or transforming growth factor-beta (TGF-beta; 10(-10) M), bone DNA synthesis activity was significantly elevated. Culture with both zinc and IGF-I enhanced additively bone DNA synthesis activity. Such an effect was not seen in the case of zinc and TGF-beta. The effect of zinc, IGF-I, or zinc plus IGF-I in increasing bone DNA synthesis activity was completely prevented by culture with PD98059 (10(-5) M), an inhibitor of mitogen-activated protein (MAP) kinase. Also, the effect of zinc, TGF-beta. or zinc plus TGF-beta in elevating bone DNA synthesis activity was significantly inhibited by culture with staurosporine (10(-6) M), an inhibitor of protein kinase C. The present study demonstrates that zinc, like bone growth factors, has a stimulatory effect on bone DNA synthesis in newborn rats.

Age Factors↗

Jansen type of spondylometaphyseal dysplasia.

Metaphyseal dysplasia, type Jansen (JMD), is a rare skeletal dysplasia with characteristic radiographic abnormalities. Of the various types of metaphyseal dysplasia, JMD shows the most severe alteration in metaphyseal architecture. All of the long tubular bones, including those of the hands and feet, show metaphyseal irregularity with a fragmented appearance and slight widening. The adjacent physes are abnormally widened, while the epiphyses tend to be slightly enlarged, rounded but otherwise normal. The spine in infancy and childhood usually appears normal. This report describes a young girl with metaphyseal changes typical of JMD except for the hands and feet, which appeared normal. She also showed very unusual abnormalities of the spine. This appears, therefore, to represent a unique osteochondrodysplasia for which we propose the term spondylometaphyseal dysplasia, type Jansen.

Abnormalities, Multiple↗

Bilateral symmetrical cysts in the upper tibiae in a skeletally mature patient: might they be simple bone cysts?

A 55-year-old Japanese woman presented with right knee pain of 1-month duration. Radiological studies revealed bilateral mild osteoarthritic changes in the medial knee joint compartment and symmetrical cysts in the upper tibial metaphyses, extending to the epiphyses. Intraosseous ganglion was considered the most probable diagnosis. However, intraoperatively, serous fluid-filled cavities were recognized; these were curetted and filled with hydroxyapatite granules. Histopathological examination of the cyst wall revealed thin fibrous tissue formed of collagen fibers without a lining cell layer, with scattered lymphocytes, histiocytes, irregular masses of fibrin-like material, and periosteal osteocartilagenous callus formation; a picture compatible with simple bone cysts. Bilateral symmetrical cysts of the upper tibial metaphyses extending to the epiphyses are extremely rare. A literature review revealed that the age incidence, and bony locations of multiple and epiphyseal simple bone cysts are atypical in relation to the classic metaphyseal simple bone cysts. Also, multiple and epiphyseal simple bone cysts have a better prognosis than the classic metaphyseal ones. Four clinicoanatomic varieties of simple bone cysts are recognized; classic metaphyseal, nontubular, epiphyseal, and multiple.

Bone Cysts↗

Phytocomponent p-hydroxycinnamic acid stimulates bone formation and inhibits bone resorption in rat femoral tissues in vitro.

The effect of cinnamic acid or its related compounds, which is present in many plants, on bone metabolism has not been clarified yet. The effect of cinnamic acid, p-hydroxycinnamic acid (HCA), ferulic acid, caffeic acid, or 3,4-dimethoxycinnamic acid (DCA) on bone calcium content in vitro was investigated. Rat femoral-diaphyseal (cortical bone) and -metaphyseal (trabecular bone) tissues were cultured for 48,h in Dulbecco's modified Eagle's medium (high glucose, 4.5%) supplemented with antibiotics and bovine serum albumin. The presence of HCA (10(-5) or 10(-4),M) caused a significant increase in calcium content in the diaphyseal or metaphyseal tissues. Such an effect was not observed in the presence of cinnamic acid or other compounds at the concentration of 10(-5) or 10(-4),M. Alkaline phosphatase activity and deoxyribonucleic acid (DNA) content in the diaphyseal or metaphyseal tissues was significantly increased in the presence of HCA (10(-5) or 10(-4),M). The effect of HCA (10(-4),M) in increasing calcium content, alkaline phosphatase activity, and DNA content in the diaphyseal or metaphyseal tissues was completely prevented in the presence of cycloheximide (10(-6),M), an inhibitor of protein synthesis. Thus HCA had anabolic effects on bone components. The presence of parathyroid hormone (PTH; 10(-7),M), a bone-resorbing factor, caused a significant decrease in calcium content and a corresponding elevation in medium glucose consumption, lactic acid production or tartrate-resistant acid phosphatase (TRACP) activity in the diaphyseal or metaphyseal tissues. These alterations were completely prevented in the presence of HCA (10(-5) or 10(-4),M). This study demonstrates that p-hydroxycinnamic acid (HCA) has stimulatory effects on bone formation and inhibitory effects on bone resorption in tissue culture in vitro.

Acid Phosphatase↗

Histogenesis of hyperosteoidosis in 1,25(OH)2D3-treated rats fed high levels of dietary calcium.

The purpose of this investigation was to determine by sequential quantitative morphometry the histogenesis of metaphyseal changes induced in rats fed high levels of dietary calcium and treated with pharmacologic doses of 1,25(OH)2D3. Young adult female rats were placed on a diet containing 2.5% calcium and 0.3% phosphorus and administered either ethanol or 135 ng (5 units) 1,25(OH)2D3 in ethanol IP daily for 10 days. Rats were terminated at Days 1, 2, 3, 4, 6, 8, and 10. At Day 1 the proximal tibias from rats treated with 1,25(OH)2D3 had a dramatic increase in osteoclasts/mm total trabecular surface perimeter compared with placebo-treated rats. Osteoclast numbers decreased in 1,25(OH)2D3-treated rats to the levels in placebo-treated rats by Days 3 and 4 and decreased significantly below placebo-treated levels at Days 6, 8, and 10. Active resorbing surface was significantly increased at Days 1 and 2 and decreased at Days 8 and 10 in 1,25(OH)2D3-treated rats compared with placebo-treated rats. From Day 4 through Day 10 in 1,25(OH)2D3-treated rats, there was a progressive increase in osteoblasts/mm total trabecular surface perimeter, osteoid surface, active osteoid surface, and metaphyseal osteoid. Metaphyseal osteoid increased markedly at Days 8 and 10 in 1,25(OH)2D3-treated rats and caused a significant increase in the amount of osseous tissue in the metaphysis. Metaphyseal mineralized bone, however, was not consistently affected by 1,25(OH)2D3 treatment. Serum calcium and phosphorus were elevated in 1,25(OH)2D3-treated rats at more time periods. In rats fed high levels of dietary calcium, repeated supraphysiologic doses of 1,25(OH)2D3 result in a net increase in metaphyseal osseous tissue, predominantly osteoid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Zinc enhancement of genistein's anabolic effect on bone components in elderly female rats.

1. The effect of genistein on the bone components in the femoral-metaphyseal and diaphyseal tissues of elderly female rats was investigated. 2. The oral administration of genistein (100 and 200 microg/kg body weight) for 3 days to rats caused a significant increase in alkaline phosphatase activity, deoxyribonucleic acid (DNA) and calcium contents in the femoral-metaphyseal and diaphyseal tissues. A dose of 50 microg genistein/kg appreciably increased alkaline phosphatase activity and DNA content in the metaphyseal but not the diaphyseal tissues. 3. Alkaline phosphatase activity, DNA and calcium contents in the femoral-metaphyseal and diaphyseal tissues were significantly elevated by the oral administration of zinc sulfate (5.5 mg Zn/kg) for 3 days. The effect of zinc on increasing bone DNA and calcium contents was synergistically enhanced by the simultaneous administration of genistein (100 microg/kg). 4. The stimulatory effect of zinc sulfate (10(-5) M) or genistein (10(-5) M) on bone calcium content was also seen in a culture system using the femoral-metaphyseal and diaphyseal tissues in vitro. This effect was completely prevented by the presence of cycloheximide (10(-6) M). 5. The present findings suggest that genistein has an anabolic effect on bone components and that the effect is enhanced by zinc, owing to its stimulating effect on bone protein synthesis.

Aging↗

beta-Cryptoxanthin stimulates bone formation and inhibits bone resorption in tissue culture in vitro.

The effect of beta-cryptoxanthin, which is greatly present in fruits, has not been clarified so far on bone metabolism. The effect of beta-cryptoxanthin on bone formation and bone resorption was investigated in tissue culture in vitro. Rat femoral-diaphyseal (cortical bone) and -metaphyseal (trabecular bone) tissues were cultured for 48 h in Dulbecco's modified Eagle's medium (high glucose, 4.5%) supplemented with antibiotics and bovine serum albumin. The experimental cultures contained 10(-8)-10(-5) M beta-cryptoxanthin. The presence of beta-cryptoxanthin (10(-6) or 10(-5) M) caused a significant increase in calcium content, alkaline phosphatase activity and deoxyribonucleic acid (DNA) content in the diaphyseal and metaphyseal tissues. These increases were completely prevented in the presence of cycloheximide (10(-6) M), an inhibitor of protein synthesis. beta-Carotene (10(-6) or 10(-5) M) or xantine (10(-6) or 10(-5) M) had no effect on the diaphyseal and metaphyseal calcium contents. The bone-resorbing factors parathyroid hormone (1-34) (PTH; 10(-7) M) or prostaglandin E2 (PGE2; 10(-5) M) caused a significant decrease in calcium content in the diaphyseal and metaphyseal tissues. The decrease in bone calcium content induced by PTH or PGE2 was completely inhibited by beta-cryptoxanthin (10(-8)-10(-6) M). In addition, beta-cryptoxanthin (10(-8)-10(-6) M) completely inhibited the PTH (10(-7) M)- or PGE, (10(-5) M)-induced increase in medium glucose consumption and lactic acid production by diaphyseal and metaphyseal tissues. The inhibitory effect of beta-cryptoxanthin (10(-7) M) on PTH (10(-7) M)- or PGE2 (10(-5) M)-stimulated decrease in the diaphyseal calcium content was significantly prevented in the presence of 10(-3) M vanadate, an inhibitor of protein tyrosine phosphatase. Vanadate (10(-3) M) did not have a significant effect on calcium content and lactic acid production in control bone tissues. The present study demonstrates that beta-cryptoxanthin has a direct stimulatory effect on bone formation and an inhibitory effect on bone resorption in tissue culture in vitro.

Alkaline Phosphatase↗

Natural evolution of Perthes disease: a study of 610 children under 12 years of age at disease onset.

Records and 2,634 pairs of radiographs (anteroposterior and lateral) of 610 patients with Perthes disease were reviewed. The evolution of the disease was divided into seven stages (stages Ia, Ib, IIa, IIb, IIIa, IIIb, and IV) based on plain radiographic appearances. Intraobserver and interobserver reproducibility of this new classification system was assessed. The duration of each stage of the disease was noted. The stages at which epiphyseal extrusion and widening of the metaphysis occurred and the stages at which metaphyseal and acetabular changes appeared were identified. The shape and the size of the femoral head, the extent of trochanteric overgrowth, and the radius of the acetabulum were assessed in hips that had healed. The new classification system of the evolution of Perthes disease was reproducible and helped to identify when crucial events occur during the course of the disease. The median duration of each stage varied between 95 and 335 days. Epiphyseal extrusion and metaphyseal widening was modest in stages Ia, Ib, and IIa but increased dramatically after stage IIb. More than 20% extrusion occurred in 70% of the hips by stage IIIa. Metaphyseal changes were most frequently encountered in stage IIb, while acetabular changes were most prevalent in stage IIIa. At healing, only 24% of untreated patients had spherical femoral heads, while 52% had irregular femoral heads. The timing of epiphyseal extrusion, metaphyseal widening, and the appearance of adverse metaphyseal and acetabular changes suggest that femoral head deformation occurs by stage IIIa in untreated hips. Hence, if containment were to succeed, it should be achieved before this stage.

Age of Onset↗

Morphogenesis of Fusarium sp-induced tibial dyschondroplasia in chickens.

Tibial dyschondroplasia was induced in female broiler chicks by the incorporation of 2% Fusarium roseum "Alaska" culture into their starter ration. Chicks were placed on this diet at one day of age and maintained until they were killed at four days or one week. Proximal tibial physes were grossly thickened into cone-shaped masses of cartilage by one week of age. Microscopically, lesions were in both ages of treated chickens and were characterized by thickening of the transitional zone which was especially prominent in the center of the growth plate. This zone was unmineralized, avascular, and contained chondrocytes which were crenated and densely eosinophilic. The cartilage matrix was pale and contained some patchy eosinophilic foci. Four growth plates with tibial dyschondroplasia and four normal growth plates from each of the four-day and one-week-old age groups were evaluated based on the following parameters: number of metaphyseal vascular sprouts, distance between the proliferative/transitional junction and the tip of the metaphyseal vascular sprouts, width of the tips of the metaphyseal sprouts, distance between tips of adjacent metaphyseal vascular sprouts, and number of perforating vessels in the proliferative zone. The distance between the proliferative/transitional junction and the metaphyseal sprout tips was greatly increased (p less than 0.01) in the affected four-day and one-week-old chickens compared to age-matched controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of polyphenols on calcium content and alkaline phosphatase activity in rat femoral tissues in vitro.

The effect of various polyphenols on calcium content and alkaline phosphatase activity in the femoral-diaphyseal and -metaphyseal tissues of young rats in vitro was investigated. Bone tissues were cultured for 24 h in serum-free Dulbecco's modified Eagle's medium containing either vehicle or various polyphenols (10(-7) - 10(-4) M). The presence of genistein (10(-6) - 10(-4) M) caused a significant increase in calcium content and alkaline phosphatase activity in the femoral-diaphyseal and -metaphyseal tissues. Resveratrol (10(-4) m) decreased metaphyseal calcium content significantly, and it (10(-6) - 10(-4) M) had a significant inhibitory effect on diaphyseal enzyme activity. Epigallocatechin gallate (EGCg; 10(-4) M) significantly inhibited alkaline phosphatase activity in the diaphyseal and metaphyseal tissues. EGCg (10(-7) - 10(-4) M) had no effect on bone calcium content. Meanwhile, glycitein, quercetin, or catechin in the range of 10(-7) to 10(-4) ml did not have an effect on calcium content and alkaline phosphatase activity in the femoral-diaphyseal and -metaphyseal tissues. The present study suggests that a phytoestrogen genistein has a unique anabolic effect on bone calcification in vitro.

Alkaline Phosphatase↗

Effect of carotenoid on calcium content and alkaline phosphatase activity in rat femoral tissues in vitro: the unique anabolic effect of beta-cryptoxanthin.

The effects of various carotenoids and rutin on calcium content and alkaline phosphatase activity in the femoral-diaphyseal and femoral-metaphyseal tissues of young rats in vitro were investigated. Bone tissues were cultured for 48 h in serum-free Dulbecco's modified Eagle's medium containing either vehicle or a compound (10(-8)-10(-6) M). The presence of beta-cryptoxanthin (10(-7) or 10(-6) M) caused a significant increase in calcium content and alkaline phosphatase activity in the femoral-diaphyseal and femoral-metaphyseal tissues. Also, the lowest concentration (10(-8) M) of beta-cryptoxanthin used caused a significant increase in diaphyseal and metaphyseal calcium content. Lutein (10(-8)-10(-6) M) had no effect on diaphyseal and metaphyseal calcium contents and diaphyseal alkaline phosphatase activity, while 10(-7) and 10(-6) M lutein significantly decreased metaphyseal alkaline phosphatase activity. Lycopene (10(-8)-10(-6) M) or rutin (10(-8)-10(-6) M) did not have a significant effect on bone calcium content and alkaline phosphatase activity. The present study suggests that the carotenoid beta-cryptoxanthin has a unique anabolic effect on bone calcification in vitro.

Alkaline Phosphatase↗

Synergistic effect of beta-cryptoxanthin and zinc sulfate on the bone component in rat femoral tissues in vitro: the unique anabolic effect with zinc.

The effect of the combination of beta-cryptoxanthin and zinc sulfate (zinc) on bone components in the femoral-diaphyseal and -metaphyseal tissues of young rats in vitro was investigated. Bone tissues were cultured for 48 h in a serum-free Dulbecco's modified Eagle's medium containing either vehicle, beta-cryptoxanthin (10(-9)-10(-7) M) or zinc sulfate (10(-6)-10(-4) M). The presence of beta-cryptoxanthin (10(-9) M) or zinc (10(-6) M) did not have a significant effect on calcium content in the femoral-diaphyseal or -metaphyseal tissues. However, culture which combined beta-cryptoxanthin (10(-9) M) and zinc (10(-6) M) caused a significant increase in calcium content in the femoral-diaphyseal and -metaphyseal tissues. Such an effect was not observed by the combination of beta-cryptoxanthin (10(-9) M) plus genistein (10(-6) M) or menaquinone-7 (10(-6) M), or zinc (10(-6) M) plus genistein (10(-6) M) or menaquinone-7 (10(-6) M). Also, the combination of beta-cryptoxanthin (10(-9) M) plus zinc (10(-6) M) caused a remarkable increase in alkaline phosphatase activity and deoxyribonucleic acid (DNA) in the femoral-diaphyseal and -metaphyseal tissues, while their application alone did not have an effect on the enzyme activity or DNA content in the femoral tissues. The effect of the combination of beta-cryptoxanthin (10(-9) M) plus zinc (10(-6) M) in increasing calcium content, alkaline phosphatase activity, and DNA content in the femoral-diaphyseal and -metaphyseal tissues was completely prevented in the presence of cycloheximide (10(-6) M), an inhibitor of protein synthesis, or 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DBR), an inhibitor of transcriptional activity. This study demonstrates that the combination of beta-cryptoxanthin and zinc at a lower concentration has a synergistic effect on bone components in vitro.

Alkaline Phosphatase↗

Alendronate administration and skeletal response during chronic alcohol intake in the adolescent male rat.

Alendronate is an aminobisphosphonate that inhibits bone resorption in osteoporotic humans and rats but does not induce osteomalacia. Several bisphosphonates, including alendronate, also have direct positive actions on osteoblasts, bone formation, and mineralization. We studied the effects of alendronate on skeletal development in adolescent male rats during chronic alcohol intake. Four groups of age- and weight-matched male Sprague-Dawley rats (35 days of age) were fed the Lieber-DeCarli diet containing 36% of calories as EtOH (E), the EtOH diet plus 60 mg/kg alendronate (EA) every other day intraperitoneally (ip), an isocaloric diet (I), or the isocaloric diet plus 60 mg/kg alendronate (IA) every other day ip. Body weight, femur length, serum levels of osteocalcin (OC), insulin-like growth factor 1 (IGF-1), testosterone, and luteinizing hormone (LH); femur distal metaphyseal and middiaphyseal bone mineral density (BMD) and tibial metaphyseal gene expression for alpha-1-type I collagen (Col I), OC, and bone alkaline phosphatase (AP); and femur strength by four-point bending to failure were measured after 28 days of feeding and alendronate injections. Serum alcohol levels at death were 156 +/- 13 mg/dl (E) and 203 +/- 40 mg/dl (EA). Alendronate given to alcohol-fed rats increased metaphyseal BMD by more than 3-fold over rats fed alcohol alone. Alendronate given to isocaloric pair-fed rats increased metaphyseal BMD by more than 2.5-fold over rats fed the isocaloric diet alone. Cortical BMD was reduced by alcohol but was increased by alendronate. Alcohol consumption reduced serum IGF-1 levels, and alendronate increased IGF-1 levels in alcohol-fed rats. Serum OC, testosterone, and LH were unaffected by alcohol and alendronate. Quantitative dot blot hybridization using rat complementary DNA (cDNA) probes and normalization against 18S subunit ribosomal RNA (rRNA) levels revealed no changes in tibial metaphyseal gene expression for type I collagen, osteocalcin, or alkaline phosphatase. Alcohol significantly reduced the biomechanical properties of the femurs that were partially compensated by alendronate. Chronic alcohol consumption uncouples formation from ongoing resorption, and resorption is inhibited by alendronate. However, alendronate's positive effects on osteoblast-mediated mineralization during chronic alcohol consumption point to the potential use of bisphosphonates in the treatment of decreased bone formation secondary to alcohol-induced diminished osteoblast function.

Alcoholism↗

Mechanisms responsible for longitudinal growth of the cortex: coalescence of trabecular bone into cortical bone.

BACKGROUND: The purpose of the present study was to determine whether longitudinal growth of the cortex occurs through intramembranous bone formation involving the periosteum or through endochondral bone formation involving the growth plate and to explore the cellular and biochemical mechanisms responsible for this process. METHODS: Cortical bone formation was studied in the metaphyses of growing New Zealand White rabbits by means of (1) oxytetracycline labeling and fluorescence microscopy, (2) computer-assisted histomorphometry, (3) osteoblast culture and [(3) H]-thymidine incorporation in the presence of periosteum or periosteum-conditioned medium, and (4) surgical insertion of membranes between the periosteum and the underlying spongiosa. RESULTS: Within the metaphyseal cortex, oxytetracycline labeling produced fluorescent closed curves outlining enlarging trabeculae derived from coalescing endochondral trabecular bone. In this region of coalescing trabeculae close to the periosteum, osteoblast surface was increased compared with trabeculae farther from the periosteum (p < 0.001). The osteoclast surface did not differ. In vitro, osteoblast proliferation was increased in the presence of periosteum (p < 0.001) or periosteum-conditioned medium (p < 0.001). Surgical insertion of permeable or impermeable membranes between the periosteum and the spongiosa did not prevent cortex formation. CONCLUSIONS: These observations demonstrate that metaphyseal cortical bone is formed by coalescence of endochondral trabecular bone. This coalescence is associated with increased osteoblast surface in the peripheral spongiosa. The increased osteoblast surface could be due to inductive effects of periosteum; in the present study, periosteum stimulated osteoblast proliferation in vitro but was not required for metaphyseal cortical bone formation in vivo. CLINICAL RELEVANCE: Understanding metaphyseal cortical growth may help to elucidate the pathophysiology of osseous growth disorders in children.

Analysis of Variance↗

Long-term follow-up of skeletal dysplasia in thalassaemia major.

We report skeletal changes due to deferoxamine (DF) in 15/29 patients with transfusion-dependent thalassaemia major (TM), followed longitudinally for growth assessment. Clinically the earliest signs were decline in height and/or sitting height growth rate, leg and back pain with restricted movement and limb deformity. Radiologically metaphyseal and spinal changes were seen in 5 subjects and vertebral lesions alone in 10. The metaphyseal changes were mild, moderate or severe and affected all long bones, but were most pronounced at wrists and knees. They progressed from widening of the growth plate and defects of metaphyseal margins to appearance of radiolucent pseudocystic areas and, in severe cases, of cupped, rickets-like metaphyses. The spinal changes proceeded from osseous defects of ventral upper and lower edges of vertebrae and biconvex contours of end-plates to platyspondyly with decreased vertebral body height. After DF dose reduction, metaphyseal changes regressed in 2 patients, while they progressed in 3, requiring corrective surgery for severe valgus knee. Spinal abnormalities either remained unchanged or progressed. Final height was very short in patients with spondylometaphyseal lesions, short and disproportionate in patients with only spinal involvement.

Adolescent↗