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PubMed1997

[Rehabilitation for musculoskeltal disorders in geriatric patients].

Aging is typically accompanied by gradual but progressive physiological changes and an increased prevalence of acute and chronic illness in any organs. Musculoskeltal system is one of the most involved organs in geriatric patients. Appropriate roles in geriatric rehabilitation for musculoskeltal disorders should be emphasized not only to treat the disorders, but also to prevent many complications cause by specific disease or injury. Representative management methods in geriatric rehabilitation are introduced in this section. Rest is often effective, especially in the acute phase of illness or injury. However, cautions should be paid in disuse syndrome which may be produced by prolonged bed rest. Major manifestations in this syndrome includes muscle weakness and atrophy, joint contracture, decubitus, osteoporosis, ectopic ossification, cardiovascular impairment, pneumonia, urological and mental problems. Physical agents such as heat, cold, light and pressure have been used as therapeutic agents. Electrical stimulation is often effective in the treatment of low-back pain syndrome. Traction is the act of drawing, or a pulling force. Its mechanism to relieve pain seems to immobilize the injured parts, to increase peripheral circulation by massage effect and to improve muscle spasm. Brace is very effective to control acute pain in musculoskeltal system. However, long-term wear of brace should be avoided to prevent the disuse syndrome. Exercise is one of the most important rehabilitation modalities. This includes stretching and muscle strengthening programs. Education of body mechanism in activity of daily living is essential in rehabilitation of geriatric patients.

Activities of Daily Living↗

PubMed2000

Genetic models reveal that brain natriuretic peptide can signal through different tissue-specific receptor-mediated pathways.

Brain natriuretic peptide (BNP), a hormone produced primarily by the cardiac ventricle, is thought to be involved in a variety of homeostatic processes through its cognate receptor, guanylyl cyclase A (GC-A). We previously created transgenic mice overexpressing BNP under the control of the liver-specific human serum amyloid P component promoter (BNP-transgenic mice) and demonstrated that they exhibit reduced blood pressure and cardiac weight accompanied by an elevation of plasma cGMP concentrations and marked skeletal overgrowth through the activation of endochondral ossification. To address whether BNP exerts its biological effects solely through GC-A, we produced BNP-transgenic mice lacking GC-A (BNP-Tg/GC-A-/- mice) and examined their cardiovascular and skeletal phenotypes. The GC-A-/- mice are hypertensive with cardiac hypertrophyrelative to wild-type littermates, which is not alleviated by overexpression of BNP in BNP-Tg/GC-A-/- mice. The BNP-Tg/GC-A-/- mice, however, continue to exhibit marked longitudinal growth of vertebrae and long bones comparably to BNP-Tg mice. This study provides genetic evidence that BNP reduces blood pressure and cardiac weight through GC-A, whereas it dramatically alters endochondral ossification in the absence of this receptor. Therefore, the BNP-Tg/GC-A-/- mice provide the first experimental model demonstrating that this natriuretic peptide can signal in a tissue-specific manner through a receptor other than GC-A.

Animals↗

PubMed1999

Acrodysplasia, severe ossification abnormalities with short stature, and fibular hypoplasia.

We present a girl with short stature, growth hormone neurosecretory dysfunction, severe hypoplastic/aplastic changes of the bones of the hands and feet with dysharmonic ossification, severely delayed bone age, microcrania, and fibular hypoplasia. Parental consanguinity suggests autosomal recessive inheritance. An additional three cases [Eiken et al., 1984: Eur J Pediatr 141: 231-235] sharing some of the radiographic manifestations of this patient have been reported. However, distinctive findings in the present case seem to outline a separate entity.

Age Determination by Skeleton↗

PubMedDate not supplied

Enalapril: pharmacokinetic/dynamic inferences for comparative developmental toxicity. A review.

Enalapril is an antihypertensive drug of the class of angiotensin-converting enzyme inhibitors (ACEI) used in pregnancy for treatment of pre-existing or pregnancy-induced hypertension. The use of ACE inhibitors (drugs that act directly on the renin-angiotensin system) during the second and third trimester of pregnancy in humans is associated with specific fetal and neonatal injury. The syndrome, termed "ACEI fetopathy" in humans, does not appear to have a similar counterpart in experimental animals. The present paper reviews pharmacokinetic and pharmacodynamic aspects of enalapril that are physiologically important during pregnancy and intrauterine development in humans and in experimental animal species with the aim of better understanding the comparability of the manifestations of enalapril developmental toxicity in animals and humans. The human fetus is at a disadvantage with regard to in utero enalapril exposure in comparison to some of the animal species for which gestational pharmacokinetic data are available. Important reasons for the higher vulnerability of the human fetus are its accessibility by enalapril and the earlier (relative to animal species) intrauterine development of organ systems that are specific targets of ACEI pharmacologic effect (the kidney and the renin-angiotensin system). In humans, these systems develop prior to calcarial ossification at the end of first trimester of pregnancy. The specific pharmacodynamic action of enalapril on these systems during fetal life is the chief determinant of the etiology and pathogenesis of ACEI fetopathy in humans. In contrast, in most of the studied animal species, these target systems are not developed until close to term when the fetus is relatively more mature (and therefore less vulnerable), so that the window of vulnerability is narrower in comparison to the human. Among animal species, the best concordance in fetal pharmacodynamics to the human is seen in the rhesus monkey, but further studies are necessary to determine if similar developmental pathology is induced in this animal model upon repeated administration of the drug during the relevant period of intrauterine development. Animal-human concordance of developmental toxicity is least likely in the rat because of greater disparities in enalapril availability to the fetus and the relative development of the kidney and skeletal ossification compared to that in humans.

Adult↗

PubMed1997

Current concepts in the treatment of articular cartilage defects.

Over time, articular cartilage loses the capacity to regenerate itself, making repair of articular surfaces difficult. Lavage and debridement may offer temporary relief of pain for up to 4.5 years, but offer no prospect of long-term cure. Likewise, marrow-stimulation techniques such as drilling, microfracture, or abrasion arthroplasty fail to yield long-term solutions because they typically promote the development of fibrocartilage. Fibrocartilage lacks the durability and many of the mechanical properties of the hyaline cartilage that normally covers articular surfaces. Repair tissue resembling hyaline cartilage can be induced to fill in articular defects by using perichondrial and periosteal grafts. However, these techniques are limited by the amount of tissue available for grafting and the tendency toward ossification of the repair tissue. Autogenous osteochondral arthroscopically implanted grafts (mosaicplasty), or open implantation of lateral patellar facet (Outerbridge technique), requires violation of subchondral bone. Osteochondral allografts risk viral transmission of disease and low chondrocyte viability, in addition to removal of host bone for implantation. Autologous chondrocyte implantation offers the opportunity to achieve biologic repair, enabling the surgeon to repair the joint surface with autologous articular cartilage. With this technique, care must be taken to ensure the safety, viability, and microbial integrity of the autologous cells while they are expanded in culture over a 4- to 5-week period prior to implantation. Surgical implantation requires equal attention to meticulous technique. In the future, physiologic repair also may become possible using mesenchymal stem cells or chondrocytes delivered surgically in an ex vivo-derived matrix. This would allow in vitro manipulation of cells with growth factors, mechanical stimuli, and matrix sizing to allow implantation of mature biosynthetic grafts which would allow treatment of larger defects with decreased rehabilitation and morbidity.

Cartilage, Articular↗

PubMed2005

Zoledronic acid improves femoral head sphericity in a rat model of perthes disease.

We hypothesized that the bisphosphonate zoledronic acid (ZA) could improve femoral head sphericity in Perthes disease by changing the balance between bone resorption and new bone formation. This study tests the effect of ZA in an established model of Perthes disease, the spontaneously hypertensive rat (SHR). One hundred and twenty 4-week old SHR rats were divided into three groups of 40: saline monthly, 0.015 mg/kg ZA weekly, or 0.05 mg/kg ZA monthly. At 15 weeks DXA measurements documented that femoral head BMD was increased by 18% in ZA weekly and 21% in ZA monthly compared to controls (p<0.01). Femoral head sphericity in animals with osteonecrosis was improved in ZA-treatment groups (p<0.01) as measured by epiphyseal quotient (EQ). The proportion of "flat" heads (EQ0.40) was significantly reduced from 32% in saline-treated animals to 12% in weekly ZA and 3% in monthly ZA (p<0.01). Histologically there was a similar prevalence of osteonecrosis in all groups. The prevalence of ossification delay was significantly reduced by ZA treatment (p<0.01). Zoledronic acid favorably altered femoral head shape in this spontaneous model of osteonecrosis in growing rats. Translation of these results to Perthes disease could mean that deformity of the femoral head may be modified in children, perhaps reducing the need for surgical intervention in childhood and adult life.

Animals↗

PubMed2000

Effects of ethnicity on skeletal maturation: consequences for forensic age estimations.

An X-ray of the hand is an important method in forensic science for estimation of the age of juvenile suspects with uncertain date of birth. Relevant X-ray standards for evaluation of skeletal maturity are available for white US Americans as well as for North and Central Europeans. The applicability of these standards to members of ethnic groups different from the reference population has been the subject of controversial discussion. More than 80 publications were analysed with the view to finding out whether skeletal maturation is affected by ethnic identity. It was concluded that skeletal maturation takes place in phases which are identically defined for all ethnic groups. Time-related differences in passing those stages of skeletal maturation within the relevant age group appear to be unaffected by ethnic identity. It is the socioeconomic status of a given population which is of decisive importance to the rate of ossification. The application of X-ray standards to individuals of a socio-economic status lower than that of the reference population usually leads to underestimation of that person's age. In terms of criminal responsibility, this is of no adverse effect on the person concerned.

Adolescent↗

PubMed2005

Expression of matrix metalloproteinase genes in the rat intramembranous bone during postnatal growth and upon mechanical stresses.

A cranial suture consists of neural-crest derived cells and matrices between mineralized skull bones. Little is known regarding the involvement of matrix metalloproteinases (MMPs) in the degradation of extracellular matrix of cranial sutures. In the postnatal rat model, the posterior frontal suture (PFS) undergoes complete ossification between P12-P22, whereas the sagittal suture (SS) remains patent. The present study utilized reverse transcriptase-polymerase chain reaction (RT-PCR) to explore the expression of MMP-1 and MMP-2 genes in the PFS and SS in P8 and P32 rats, and also to determine whether these MMP genes are modulated by exogenous mechanical forces. RNA was isolated from P8 and P32 normal PFS and SS each by pooling sutural specimens from 14 to 20 rats. RT-PCR analysis and semi-quantitative luminosity demonstrated the expression of MMP-1 and MMP-2 genes in the patent P8 PFS, P8 SS, and P32 SS, but no apparent MMP-2 expression in the physiologically ossified P32 PFS. Exogenous cyclic forces applied to the maxilla at 1000 mN and 4 Hz elicited corresponding cyclic bone strain waveforms with peak strain of 134.14+/-38.15 muepsilon (mean+/-S.D.) for the PFS, and 28.35+/-10.86 muepsilon for the SS in P32 rats. These cyclic forces delivered for 20 min/d over 2 consecutive days induced the expression of MMP-2 gene in the physiologically fused P32 PFS that was not expressed without mechanical stresses. Taken together, these data suggest potentially important roles of MMP genes in the postnatal development of cranial sutures, and their susceptibility to mechanical stresses.

Animals↗

PubMed1986

A longitudinal study of carpal bone development in Perthes' disease: its significance for both radiologic standstill and bilateral disease.

This paper reports a longitudinal study of carpal bone development in 125 children (98 boys, 27 girls) attending a clinic for Perthes' disease. The age at appearance of ossification in each carpal bone was estimated by studying consecutive radiographs obtained at six-months intervals. The results were compared with the findings for normal children published by Stuart et al. Three radiologic groups of carpal bone maturation are defined: not delayed (capitate and hamate); markedly delayed (triquetral and lunate); and slightly delayed (scaphoid, trapezium, and trapezoid). Overall, the bone age delay is severely abnormal at three to five years of chronologic age and indicates the time in development when general abnormalities occur. The mean age at diagnosis (and standard deviation) for 34 boys with skeletal standstill was 4.49 +/- 1.07 years, compared with 7.28 +/- 2.40 years for 51 boys without such standstill; the mean age at appearance of carpal bones was not significantly different between these two groups, suggesting an equally profound delay of carpal maturation in the group of later-diagnosed boys. Boys with bilateral hip disease show a significant delay in age at ossification of the trapezoid compared with boys who have unilateral disease. The immaturity of bone age may be present during a latent period and be of etiologic significance in the onset of the hip disease, but at present the evidence links it only with bilateral disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Carpal Bones↗

PubMed1998

Switch of osteonectin and osteopontin mRNA expression in the process of cartilage-to-bone transition during fracture repair.

The process of cartilage-to-bone transition (CBT) is a key event for the achievement of rigid bone healing during fracture repair. Since mineralization of cartilaginous matrix is a prerequisite for the initiation of CBT, the genetic localization of mineralization-related bone matrix proteins in CBT was examined in this study. An in situ hybridization method used on decalcified sections with digoxigenin-11-UTP labelled probes identified the cellular localizations of these genes in CBT. Cessation of osteonectin mRNA together with induction of osteopontin mRNA in chondrocyte maturation was observed during the process of CBT in the fracture callus on day 12 after fracture; osteocalcin mRNA was absent in chondrocytes of the CBT area. Induction of osteopontin mRNA in maturated chondrocytes was followed by the expression of mRNAs for osteonectin, osteopontin and osteocalcin in osteogenic cells in the ossification front of CBT. The data suggest that the switch from osteonectin to osteopontin mRNA expression in chondrocyte maturation is one of the key events during CBT. Transcriptional disorders of the expression of these molecules may be linked to the failure of fracture repair, i.e. delayed or prevented hypertrophic osteosynthesis.

Animals↗

PubMed1990

[Matrix vesicles in membranous ossification].

Calcification process in membranous ossification was examined histologically by light and electron microscopies in comparison with that in enchondral ossification. The following results were obtained: 1) In the rat tibial articular cartilage, the extracellular matrix proceeding from the transitional to the hypertrophic zone consisted of the following three layers from the proximal: the first layer in which ruthenium red positive granules were densely populated and thin collagen fibrils diffusely arranged but few matrix vesicles were observed; the second one containing numerous matrix vesicles and slightly thick collagen fibrils; and the last one in which the thick collagen fibrils were observed while matrix vesicles and ruthenium red positive granules were few. 2) In the calcified regions in the extracellular matrix of MC3T3-E1 cells, the regions of alveolar new bone formation due to orthodontic tooth movement and the calcified regions in the interparietal suture expanded mechanically in vitro, the number of matrix vesicles was less than those in the regions of enchondral ossification. 3) Ruthenium red positive granules were fewer in the regions of alveolar new bone formation after the orthodontic tooth movement than in the calcified regions of cartilage. 4) The observation on MC3T3-E1 cells revealed the two different possibilities of the processes of calcification: the calcification induced by matrix vesicles as an initiator and that directly related to mineral deposit on the collagen fibrils.

Alveolar Process↗

PubMed1992

[Enhancement of the ossification of decalcified bone].

Authors have proven with previous experiments that the decalcinated bone can be used as transplant. In this paper their experiments to increase the osteogene capacity of this kind of bone for replacement are described. It is stated that with the use of electric after treatment both the speed of the development of new bone after bone replacement both the rebuilding on the recipient bone ends may be advantageously influenced. With their method the bone defect in the rabbit's radius could be healed in four weeks.

Animals↗

PubMedDate not supplied

Fractures and rickets in very low birth weight infants: conservative management and outcome.

Fractures and rickets (F/R) often occur in very low birth weight (VLBW less than 1500 g) infants who are acutely ill. However, there are no prospective longitudinal studies of the clinical course of F/R in these infants. In a prospective study of 78 VLBW infants during the first year after birth, radiographic evidence of healing and remodeling of F/R was noted in affected infants (n = 25) concurrent with increased enteral intake and physical growth, and regardless of whether specific orthopedic treatment was initiated. Skeletal maturation as indicated by the development of ossification centers at the wrists was directly related to weight gain, and was similar to term infants by 1 year. No infant had skeletal deformities on follow-up examination. We suggest that VLBW infants with F/R can be managed "conservatively," with emphasis on nutritional intake to achieve weight gain.

Bone Development↗

PubMed1998

Mice lacking smooth muscle calponin display increased bone formation that is associated with enhancement of bone morphogenetic protein responses.

BACKGROUND: Calponin is a calmodulin-and actin-binding protein expressed in smooth muscle. It promotes actin polymerization and inhibits actin-activated myosin ATPase activity. Despite the molecular and functional characterization of calponin in vitro, the physiological role of calponin in vivo has not been clarified. RESULTS: We investigated the in vivo function of smooth muscle calponin (also called basic calponin or calponin h1) by generating mice carrying a targeted mutation in both alleles of the calponin gene. Mice lacking basic calponin expression displayed enhanced ectopic bone formation in vivo, induced by recombinant human bone morphogenetic protein-2 (rhBMP-2), and an augmentation of the degree of osteoblastic differentiation of embryonic mesenchymal cells when they were stimulated by rhBMP-2. Basic calponin messenger RNA was shown to be expressed in developing and healing bone tissues, and in undifferentiated MC3T3-E1 osteoblasts. An examination of the skeletons of mutated mice showed an early onset of cartilage formation and ossification, and increased postnatal bone formation characterized by an increase in the number of activated periosteal osteoblasts. Bone fracture healing was accelerated in mutated mice. CONCLUSION: This is the first demonstration of animals with enhanced BMP responsiveness in host cells, suggesting that endogenous basic calponin may play a negative role in an osteogenic programme.

Animals↗

PubMed1989

Analyses of the tidemark on human femoral heads. II. Tidemark changes in osteoarthrosis--a histological and histomorphometric study in non-decalcified preparations.

Histological and histomorphometric examinations were carried out on 88 human femoral heads, 63 from patients with osteoarthrosis and 25 controls. The changes of the tidemark were found to be multiform in the osteoarthrotic process and could be classified into three degrees of severity. Low-grade tidemark changes were characterized by reduplications of the tidemark and discontinuities of the tidemark line, occurring also in about one third of the controls. Vascular invasion into the tidemark as well as incipient calcification of basal hyaline cartilage were observed in middle-grade tidemark alterations. High-grade changes were distinguished by the disappearance of the tide-mark, advanced mineralization and ossification of basal hyaline and calcified cartilage and finally by the "tidemark and bone bald". Measuring the thickness of intact and osteoarthrotic hyaline cartilage, calcified layer and subchondral bone plate, it was possible to determine some correlations between the tidemark state and the structures measured. Variations in subchondral bone volume could also influence the tidemark and cartilage changes. The important role of the intercartilaginous junction in the pathogenesis and progress of osteoarthrosis is stressed.

Aged↗

PubMed2004

Distal humeral fractures treated with noncustom total elbow replacement.

BACKGROUND: The purpose of this study was to review the cases of patients with a distal humeral fracture that was treated with a noncustom total elbow arthroplasty. We hypothesized that, on the basis of the functional and clinical outcome, total elbow replacement is a reliable option for the treatment of elderly patients with a severe, comminuted fracture of the distal part of the humerus. METHODS: We retrospectively reviewed forty-nine acute distal humeral fractures in forty-eight patients who were treated with total elbow arthroplasty as the primary option. The average age of the patients was sixty-seven years. Forty-three fractures were followed for at least two years. According to the AO classification, five fractures were type A, five were type B, and thirty-three were type C. The average age of the forty-three patients was sixty-nine years and the average duration of follow-up was seven years. Fourteen patients died during the review period. Postoperative clinical function was assessed with use of the Mayo elbow performance score, and anteroposterior and lateral radiographs made at follow-up examinations were reviewed. RESULTS: At the latest follow-up examination, the average flexion arc was 24 degrees (range, 0 degrees to 75 degrees ) to 131 degrees (range, 100 degrees to 150 degrees ) and the Mayo elbow performance score averaged 93 of a possible 100 points. Heterotopic ossification was present to some extent in seven elbows, with radiographic abutment noted in two. Thirty-two (65%) of the forty-nine elbows had neither a complication nor any further surgery from the time of the index arthroplasty to the most recent follow-up evaluation. Fourteen elbows (29%) had a single complication, and most of them did not require further surgery. Ten additional procedures, including five revision arthroplasties, were required in nine elbows; five were related to soft tissue and five were related to the implant or bone. CONCLUSIONS: Complex distal humeral fractures should be assessed primarily for the reliability with which they can be reconstructed with osteosynthesis. When osteosynthesis is not considered to be feasible, especially in patients who are physiologically older and place lower demands on the joint, total elbow arthroplasty can be considered. This retrospective review supports a recommendation for total elbow arthroplasty for the treatment of an acute distal humeral fracture when strict inclusion criteria are observed.

Adult↗

PubMed2005

Distal humeral fractures treated with noncustom total elbow replacement. Surgical technique.

Arthroplasty, Replacement↗

PubMed1992

Effects of an augmented nerve supply on forelimb regeneration in the adult mud frog, Rana rugosa.

Forelimbs of the adult mud frog Rana rugosa, when amputated midway through the zeugopodium, regenerate heteromorphically. The resulting regenerative outgrowths were mostly rod shaped and consisted of a cartilaginous core, in which the base was ossified, and muscle elongated distally along the cartilage, the whole being covered by connective tissue and skin. The tip of the regenerating muscle reached a point distally about one third of the length of the regenerative outgrowths. When the innervation of forelimb stumps was augmented by surgical diversion of the ipsilateral sciatic nerve, the amputated limbs regenerated mostly as spatula-shaped outgrowths, which were longer than those of normally innervated forelimbs. Such hyperinnervated regenerates exhibited less ossification of cartilage, or sometimes none at all. However, the regeneration of muscle was more extensive. That is, it reached more than half way along the regenerative outgrowth. Furthermore, denervation resulted in the absence of regeneration in all cases examined. These results clearly indicate that limb regeneration in Rana rugosa is dependent upon the degree of innervation, not only for the early stages of regeneration, but also for the growth and differentiation of the regenerative outgrowth.

Animals↗